Background: Coronary artery bypass grafting (CABG) is a well-established procedure for treating diabetic patients with multivessel disease, but extracorporeal circulation and cardioplegia-induced cardiac arrest introduce a severe burden to these patients. The present study investigated if off-pump CABG decreases 30-day mortality and mid-term mortality in diabetic patients in comparison with conventional CABG. Methods: From February 2009 through October 2011, data from 355 consecutive adult diabetic patients undergoing off-pump CABG and 502 patients undergoing on-pump CABG were prospectively recorded. Data analysis was performed by propensity score (PS)-adjusted logistic regression analysis and PS-adjusted Cox regression analysis. The primary endpoint was 30-day mortality. Secondary endpoints were major complications and mortality on follow-up. Results: Off-pump CABG was associated with a significantly lower 30-day mortality rate (0.3% vs 4.2%; adjusted odds ratio [OR] = 0.09 [95% confidence interval (CI):0.01 to 0.70] p = 0.021) than on-pump CABG. Results coincided with a lower rate of postoperative neurologic complications in patients undergoing off-pump CABG (1.7% vs 5.4%; adjusted OR = 0.31 [95% CI: 0.12 to 0.77] p = 0.012) and a less frequent need for hemofiltration in these patients (3.4% vs 10.4%; adjusted OR = 0.30 [95% CI: 0.14 to 0.64] p = 0.002). The off-pump technique decreased the 6-month mortality rate (2.3% vs 8.8%; adjusted hazard ratio = 0.27 [95% CI: 0.12 to 0.61] p = 0.002) and also the 1-year mortality rate (4.0% vs 10.6%; adjusted hazard ratio = 0.40 [95% CI: 0.22 to 0.75] p = 0.004) significantly. Conclusions: Our data indicate that in terms of postoperative complications and early and mid-term survival, off-pump CABG is superior to the on-pump technique in diabetic patients.