Objective Octogenarians, as the fastest growing stratum of the population and with the highest prevalence of coronary artery disease, are being increasingly referred for coronary artery bypass grafting (CABG). The general perception is that the presence of comorbidities and the propensity for neurological injury expose them to a higher risk for mortality and morbidity after conventional on-pump CABG, and therefore, off-pump CABG should be preferentially offered to octogenarians to improve outcomes. This study evaluates the in-hospital outcomes and predictors of mortality and stroke in octogenarians undergoing on- and off-pump CABG at our institution. Methods From January 2000 to December 2010, a total of 290 octogenarians underwent off-pump (n = 217) and on-pump (n = 73) CABG. Their data were prospectively entered into the cardiac surgery database (Patients Analysis & Tracking System; Dendrite Clinical Systems, Ltd, Oxford, England, United Kingdom) and analyzed retrospectively. Outcome measures included in-hospital mortality, major complications, and length of stay. Multivariate analysis was performed to identify predictors of combined outcome of in-hospital mortality and stroke. Results The mean ± SD age of the patients was 82 ± 2.0 years. Preoperative demographics were similar for the on-pump and off-pump groups. The patients who underwent off-pump CABG had a lower number of distal anastomoses performed compared with the patients who underwent on-pump CABG [mean difference, 0.2; 95% confidence interval (CI), 0.02–0.4; P = 0.03]. However, the ratio of grafts (received/needed) was the same in both groups. In-hospital mortality for the entire cohort was 7.2%, with no significant difference between the groups for death (6.0% vs 11.0%; P = 0.08), stroke (2.8% vs 2.8%; P = 1.0), other major complications, and length of hospital stay. Independent predictors of combined outcome identified from the multiple logistic model included heart failure [odds ratio (OR), 4.4; 95% CI, 1.5–13.0; P = 0.008], diabetes (OR, 2.6; 95% CI, 1.0–6.0; P = 0.046), nitrate infusion (OR, 2.9; 95% CI, 1.1–8.0; P = 0.04), postoperative renal failure requiring hemofiltration (OR, 8.6; 95% CI, 3.5–21.1; P < 0.001), and postoperative ventricular arrhythmias (OR, 7.3; 95% CI, 1.9–27.8; P = 0.009). Conclusions Both on-pump and off-pump CABG are reasonable revascularization strategies in octogenarians. Careful patient selection and individualized treatment decisions can minimize postoperative mortality and morbidity in octogenarians undergoing on- and off-pump CABG.