DNA analysis played a pivotal forensic role in the O.J. Simpson case, marking one of the earliest instances where DNA evidence was heavily relied upon in a high-profile trial. Blood samples were collected from multiple locations, including the crime scene, Simpson's white Ford Bronco, his residence, and various clothing items. Among the key pieces of evidence were a pair of socks found in Simpson's bedroom that contained blood matching Nicole Brown Simpson's DNA. Additionally, two blood-stained leather gloves were discovered: one at Simpson's estate and the other at the crime scene. Analysis of these gloves showed DNA markers linking them to both victims and Simpson himself, suggesting a direct physical connection to the murders. DNA profiling techniques were used to analyze blood found at the crime scene, in Simpson’s Bronco, and on clothing items. The results showed a mixture of Simpson's blood and the blood of both Nicole Brown Simpson and Ron Goldman. This evidence seemed to place Simpson at the scene and indicated potential contact with the victims after their injuries. However, the defense raised serious concerns about the handling of this evidence. They argued that contamination and mishandling by law enforcement had compromised the integrity of the samples, potentially skewing results. For example, the defense pointed to inconsistencies in the chain of custody and alleged that improper storage and transport could have led to contamination, an argument that resonated with many jurors. Despite the scientific rigor behind DNA analysis, the defense's arguments regarding possible mishandling and cross-contamination created doubt. This, combined with broader issues of racial tension and alleged misconduct within the Los Angeles Police Department, weakened the impact of the DNA evidence, ultimately contributing to Simpson’s acquittal in the criminal trial. Nonetheless, the case highlighted the power of DNA analysis in criminal investigations and underscored the importance of meticulous evidence handling practices.

Blood spatter analysis was a key forensic method used in reconstructing the sequence of events in the murders of Nicole Brown Simpson and Ron Goldman. Investigators examined blood patterns at the crime scene, particularly around the bodies, to understand the possible positions and movements of the victims and attacker during the assault. Bloodstains and drops on the walkway leading to Nicole’s front door provided insights into the struggle that likely occurred, with patterns suggesting that both victims sustained multiple injuries while attempting to defend themselves. In addition to the crime scene, blood was found on Simpson's socks in his bedroom, which matched Nicole Brown Simpson's DNA, indicating contact with her blood despite Simpson’s claim that he hadn’t seen her that evening. Blood spatter inside Simpson’s white Ford Bronco also suggested a connection to the crime. Stains inside the vehicle included a mix of Simpson’s blood along with blood from both victims, indicating that he may have been bleeding and in contact with the victims’ blood at the time or shortly after the murders. Investigators noted that the blood evidence inside the vehicle and on personal items strongly pointed to Simpson’s involvement, as the spatter patterns indicated movement that would align with someone leaving a violent scene. However, the defense argued that improper collection techniques, as well as the potential for contamination and transfer, called the reliability of the blood evidence into question. They suggested that the blood spatter evidence could have been mishandled or planted by law enforcement, a claim that stirred public debate and contributed to doubts among jurors about the integrity of the forensic process. Despite these arguments, the blood spatter evidence remained one of the most compelling pieces in the prosecution's case, illustrating how the science of blood pattern analysis can inform crime scene reconstructions and support or challenge testimonies regarding suspect movements.

Hair and fiber analysis added another layer of forensic evidence in the O.J. Simpson case, linking Simpson to the crime scene. Investigators collected hair samples and fibers from various locations, including the crime scene, Simpson's vehicle, and his personal belongings. Hair samples found on Ronald Goldman’s shirt were analyzed and matched to Simpson, suggesting physical contact between the two at or near the time of the murder. In addition to hair samples, fibers played a significant role. Fibers from the carpet in Simpson's Ford Bronco were found at the crime scene, as well as on items of clothing connected to Simpson, implying that he may have been present at the scene and transported fibers from his car. Investigators also analyzed fibers on the gloves found at the scene and at Simpson’s residence. The fibers were consistent with those from clothing items owned by Simpson, further connecting him to both the crime scene and the evidence collected. The defense argued that contamination or cross-transfer of fibers and hair could have occurred due to improper handling, suggesting that law enforcement officers might have unintentionally transferred evidence between locations. Despite these objections, the hair and fiber evidence bolstered the prosecution’s narrative of Simpson’s involvement, illustrating how these types of trace evidence can create connections between suspects, victims, and locations in forensic investigations.

Shoe print analysis provided critical evidence in the O.J. Simpson case, as investigators discovered a bloody shoe print at the crime scene that was linked to a rare, high-end Italian shoe brand, Bruno Magli. The specific shoe model, the "Lorenzo" size 12, was particularly rare in the United States, with only a limited number imported. This detail made the print highly significant since it would likely have belonged to a limited pool of owners. The prosecution used photographic evidence to establish a connection between Simpson and the Bruno Magli shoes. Initially, Simpson denied owning or ever wearing such shoes, dismissing the suggestion as untrue. However, photos later surfaced showing Simpson wearing shoes identical to the Bruno Magli model in question, which seriously undermined his denial. The shoe print found at the crime scene was consistent in size and pattern with those particular shoes, and the pattern of the print closely matched the sole of the Bruno Magli Lorenzo, linking Simpson to the scene even though no physical shoe was found in his possession. The shoe print analysis provided the jury with a tangible connection between Simpson and the crime, supporting other forensic findings such as blood, DNA, and fiber evidence. This line of evidence not only contradicted Simpson’s claims but also demonstrated the importance of footprint evidence in forensic science, especially when the item itself isn’t directly available for examination. While Simpson’s defense attempted to question the credibility of the photos showing him in the shoes, the analysis added weight to the prosecution's case by showing yet another link between Simpson and the murder scene.