Purpose <p>We aimed to investigate the impact that patient-initiated beta-blocker interruption on the morning of surgery has on postoperative adverse outcomes.</p> Methods <p>We conducted a historical cohort study of consecutive patients undergoing elective surgical procedures at two hospitals belonging to a single academic institution from 2014 to 2018 in the Canadian province of Ontario. We used electronic medical records to identify the initial cohort and collect patient information, including medication interruption. These data were linked to administrative data holdings, which we used to capture study outcomes, including 30-day and 90-day mortality and a composite outcome representing several adverse events. We used logistic regression to evaluate between-group differences in study outcomes and included a covariate representing propensity for beta-blocker interruption.</p> Results <p>The final cohort included 4,971 patients, 22.2% of whom experienced a preoperative beta-blocker interruption. As compared with patients who continued their medication, those with a beta-blocker interruption had significantly decreased odds of 30-day mortality (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.18 to 1.00; <i>P</i> = 0.049) and 90-day mortality (OR, 0.51; 95% CI, 0.28 to 0.90; <i>P</i> = 0.02) in adjusted analyses. Following adjustment, beta-blocker interruption was not significantly associated with any of the secondary outcomes.</p> Conclusions <p>Results from this study suggest that preoperative acute beta-blocker interruption is significantly associated with decreased 30-day and 90-day postoperative all-cause mortality. These data challenge the long-held assumption that patients on beta-blockers should continue these medications during the perioperative period and indicate that a proper controlled trial is needed to assess the impact of withholding beta-blockers prior to major surgery.</p>