BACKGROUND The purpose of this study was to assess the prognostic effect of coronary collaterals on early and midterm clinical outcomes in patients undergoing first time isolated off-pump coronary artery bypass (OPCAB) surgery. METHODS Preoperative angiograms from 861 patients were evaluated to assess the presence and extent of coronary collaterals (Rentrop classification). Coronary collaterals (CC) were present in 485 (56.3%) patients (CC group). Patients with coronary collaterals had a higher incidence of preoperative myocardial infarction, lower ejection fraction, and higher Parsonnet scores compared with patients without coronary collaterals (no-CC group). RESULTS Coronary collaterals were associated with myocardial protection during OPCAB surgery, as evidenced by a significantly lower incidence of intraoperative ST-segment changes (propensity matched cohort, p = 0.008). No other statistically significant differences in in-hospital outcomes were detected between the two groups. Five years after surgery patient survival was 84.8% (95% confidence interval [CI] 79.4 to 88.8) in the CC group compared with 89.2% (95% CI 84.4 to 92.6) in the no-CC group (p = 0.48). Cardiac-related event-free survival after 5 years was 50.6% (95% CI 43.5 to 57.3) in the CC group and 54.5% (95% CI 47.1 to 61.4) in the no-CC group (p = 0.96), with no significant differences between both groups, before or after risk adjustment, or when comparing propensity-matched cohort. CONCLUSIONS Although patients with coronary collaterals had more extensive coronary artery disease, poor left ventricular function, and more cardiac risk factors than patients without collaterals, the early and midterm clinical outcome after OPCAB surgery was comparable between the two groups.