When anesthesia is titrated using bispectral index (BIS) monitoring, patients generally receive lower doses of hypnotic drugs. Intraoperative hypotension and organ toxicity might be avoided if lower doses of anesthetics are administered, but whether this translates into a reduction in serious morbidity or mortality remains controversial. The B-Aware Trial randomly allocated 2463 patients at high risk of awareness to BIS-guided anesthesia or routine care. We tested the hypothesis that the risks of death, myocardial infarction (MI), and stroke would be lower in patients allocated to BIS-guided management than in those allocated to routine care. The medical records of all patients who had not died within 30 days of surgery were reviewed. The date and cause of death and occurrence of MI or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary end point of the study was survival. The median follow-up time was 4.1 (range: 0-6.5) years. Five hundred forty-eight patients (22.2%) had died since the index surgery, 220 patients (8.9%) had an MI, and 115 patients (4.7%) had a stroke. The risk of death in BIS patients was not significantly different than in routine care patients (hazard ratio = 0.86 95% confidence interval {CI}: 0.72-1.01; P = 0.07). However, propensity score analysis indicated that the hazard ratio for death in patients who recorded BIS values <40 for >5 min compared with other BIS-monitored patients was 1.41 (95% CI: 1.02-1.95; P = 0.039). In addition, the odds ratios for MI in patients who recorded BIS values <40 for >5 min compared with other BIS-monitored patients was 1.94 (95% CI: 1.12-3.35; P = 0.02) and the odds ratio for stroke was 3.23 (95% CI: 1.29-8.07; P = 0.01). Monitoring with BIS and absence of BIS values <40 for >5 min were associated with improved survival and reduced morbidity in patients enrolled in the B-Aware Trial.