Introduction: Whether anesthesia depth affects postoperative mortality remains uncertain. Measurements: Several databases were systematically searched to identify all articles studying the relationship between depth of anesthesia and postoperative mortality. Post hoc subgroup analyses were conducted for followup period (30 days vs. longer than 90 days) and type of surgery. Main results: The analysis included 38,722 patients from nine studies. We observed a significant relationship between low bispectral index (BIS) and mortality (pooled aHR, 1.22;95% CI, 1.08 to 1.38; P = 0.001; I-2 = 85.4%). Post hoc subgroup analyses indicated low BIS to be linked with significantly elevated mortality risk in patients with >= 90 days follow-up (pooled adjusted hazard ratio [aHR], 1.09; 95% CI, 1.00-1.19; P = 0.01; I-2 = 79.4%), but this association did not achieve significance in those with a 30 day follow-up duration (pooled aHR, 1.52; 95% CI, 0.97-2.38; P = 0.28; I-2 = 79.0%). In addition, this link between postoperative mortality and low BIS was significant in those who had undergone cardiac surgery (pooled aHR, 1.30; 95% CI, 1.14 to 1.49; P < 0.001; I-2 = 0.0%), but not in patients that had received other forms of surgery (pooled aHR, 1.06; 95% CI, 0.98 to 1.14; P = 0.14; I-2 = 73.2%). Conclusions: We observed a significant relationship between deep anesthesia and long-term mortality, though this was not significant 30 days following surgery. In patients who had received cardiac surgery, deep anesthesia may increase mortality. However, this trend was not observed in patients who had undergone other forms of surgery.