OBJECTIVE To investigate the effects of alpha(2)-adrenergic agonists on perioperative mortality and cardiovascular complications in adults undergoing surgery. METHODS MEDLINE (1966 to May 2002), EMBASE (1980 to May 2002), the Cochrane Clinical Trials Register, the Science Citation Index, and bibliographies of included articles were searched without language restriction. Randomized trials comparing preoperative, intraoperative, or postoperative (first 48 hours) administration of clonidine, dexmedetomidine, or mivazerol with controls were included. Studies had to report any of the following outcomes: mortality, myocardial infarction, ischemia, or supraventricular tachyarrhythmia. Treatment effects were calculated using the fixed-effects model. Heterogeneity was assessed using the Q test. RESULTS Twenty-three trials comprising 3395 patients were included. Overall, alpha(2)-adrenergic agonists reduced mortality (relative risk [RR] = 0.64; 95% confidence interval [CI]: 0.42 to 0.99; P = 0.05) and ischemia (RR = 0.76; 95% CI: 0.63 to 0.91; P = 0.003) significantly. They also reduced mortality (RR = 0.47; 95% CI: 0.25 to 0.90; P = 0.02) and myocardial infarction (RR = 0.66; 95% CI: 0.46 to 0.94; P = 0.02) during vascular surgery. During cardiac surgery, alpha(2)-adrenergic agonists reduced ischemia (RR = 0.71; 95% CI: 0.54 to 0.92; P = 0.01) and were associated with trends toward lower mortality (RR = 0.49; 95% CI: 0.12 to 1.98; P = 0.3) and a reduced risk of myocardial infarction (RR = 0.83; 95% CI: 0.35 to 1.96; P = 0.7). CONCLUSIONS Alpha-2 adrenergic agonists reduce mortality and myocardial infarction following vascular surgery. During cardiac surgery, they reduce ischemia and may also have effects on mortality and myocardial infarction. Large randomized trials are needed to evaluate these agents during cardiac and vascular surgery.