Hypothesis: This project tested the hypothesis that computer-aided decision support during the first 30 minutes of trauma resuscitation reduces management errors. Design: Ours was a prospective, open, randomized, controlled interventional study that evaluated the effect of real-time, computer-prompted, evidence-based decision and action algorithms on error occurrence during initial resuscitation between January 24, 2006, and February 25, 2008. Setting: A level I adult trauma center. Patients: Severely injured adults. Main Outcome Measures: The primary outcome variable was the error rate per patient treated as demonstrated by deviation from trauma care algorithms. Computer-assisted video audit was used to assess adherence to the algorithms. Results: A total of 1171 patients were recruited into 3 groups: 300 into a baseline control group, 436 into a concurrent control group, and 435 into the study group. There was a reduction in error rate per patient from the baseline control group to the study group (2.53 to 2.13, P=.004) and from the control group to the study group (2.30 to 2.13, P=.04). The difference in error rate per patient from the baseline control group to the concurrent control group was not statistically different (2.53 to 2.30, P=.21). A critical decision was required every 72 seconds, and error-free resuscitations were increased from 16.0% to 21.8% (P=.049) during the first 30 minutes of resuscitation. Morbidity from shock management (P=.03), blood use (P<.001), and aspiration pneumonia (P=.046) were decreased. Conclusions: Computer-aided, real-time decision support resulted in improved protocol compliance and reduced errors and morbidity. Trial Registration: clinicaltrials.gov Identifier: NCT00164034.