<p><b>Objectives:</b> Despite increasing recognition that off-pump coronary artery bypass surgery and sequential grafting strategy individually are associated with improved outcomes, concerns persist regarding the safety and efficacy of combining these 2 techniques. We compared in-hospital and midterm outcomes for off-pump multivessel sequential and conventional coronary artery bypass grafting.</p><p><b>Methods:</b> From September 1998 to September 2008, 689 consecutive patients received off-pump multivessel sequential coronary artery bypass grafting performed by a single surgeon. These patients were propensity matched to 689 patients who underwent off-pump coronary artery bypass grafting without sequential anastomoses. A retrospective analysis of prospectively collected perioperative data was performed. In addition, medical notes and charts of all the study patients were reviewed. The mean duration of follow-up was 5.1 � 2.0 years.</p><p><b>Results:</b> The major in-hospital clinical outcomes in the sequential and control groups were found to be similar. After adjusting for clinical covariates, sequential grafting was not an independent predictor of in-hospital adverse events (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.86-1.50; <i>P</i> = .31), medium-term mortality (hazard ratio [HR], 1.26; 95% CI, 1.06-1.32; <i>P</i> = .92), and readmission to hospital (HR, 1.12; 95% CI, 0.96-1.20; <i>P</i> = .80). Sequential grafting was an independent predictor of receiving more than 3 distal anastomoses (OR, 7.46; 95% CI, 4.27-11.45; <i>P</i> < .0001). Risk-adjusted survival was 89% for sequential grafting patients and 88% for conventional grafting patients (<i>P</i> = .96) during the medium-term follow-up.</p><p><b>Conclusion:</b> Our analysis confirms the short- and midterm safety and efficacy of off-pump sequential coronary artery bypass grafting.</p>