The incidence of perioperative stroke was 55 of 57,218 (0.09%). Preoperative metoprolol was associated with an approximately 4.2-fold increase in perioperative stroke (P < 0.001; 95% CI, 2.2–8.1). Analysis of matched cohorts revealed a significantly higher incidence of stroke in patients taking preoperative metoprolol compared with atenolol (P = 0.016). However, preoperative metoprolol was not an independent predictor of stroke in the entire cohort, which included patients who were not taking β blockers. The use of intraoperative metoprolol was associated with a 3.3-fold increase in perioperative stroke (P = 0.003; 95% CI, 1.4–7.8); no association was found for intraoperative esmolol or labetalol.