There has been concern regarding the safety of cardiac surgical intervention during off-hours. Sleep deprivation, resource limitations, and an increased case urgency have been postulated to increase off-hours surgical risk, although outcomes are inconsistent in the existing literature. In this systematic review and meta-analysis, we review the literature comparing patients undergoing cardiac surgery during on and off-hours. PubMed and Embase were systematically searched for literature published from January 2000-September 2023, comparing outcomes of patients undergoing cardiac surgery during on and off-hours. Overall, 3540 manuscript titles and abstracts were screened and 11 articles were included. Overall aggregate analysis indicated no significant differences in rates of in-hospital mortality(OR 1.04; 95% CI, 0.41-2.63; P=0.93) and perioperative morbidity, including stroke (P=0.52), reoperation (P=0.92), major bleeding (P=0.10), and renal complications (P=0.55). Composite rates of sternal wound infection favored on-hours surgery (P=0.01). Although inferior outcomes in patients undergoing cardiac surgery during off-hours have been noted, aggregate analysis largely revealed equivalent perioperative morbidity and mortality during on and off-hours surgery, although with the exclusion of one outlier study in-hospital mortality and reoperation favored on-hours surgery. Heterogeneity in outcomes is likely multifactorial, with surgical staff fatigue, patient preoperative risk, clinical setting, and resource limitations all contributing. Further investigation is required directly comparing emergent cardiac surgical intervention during on-hours and off-hours controlling for baseline surgical risk to elucidate the true impact of timing of surgery on postoperative outcomes.