Background The aim of this two-center, open, randomized, controlled trial was to evaluate the impact of thoracic epidural anesthesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass surgery. Methods Two hundred and twenty-six patients were randomized to either general anesthesia plus epidural (GAE) (n = 109) or general anesthesia only (GA) (n = 117). The primary outcome was length of postoperative hospital stay. Secondary outcomes were: arrhythmia, inotropic support, intubation time, perioperative myocardial infarction, neurologic events, intensive care stay, pain scores, and analgesia requirement. Results Baseline characteristics were similar in the two groups. One patient died in the GAE group. Median postoperative stay was significantly reduced in the GAE, compared with the GA, group (5 days, interquartile range [5-6] vs. 6 days, interquartile range [5-7], hazard ratio = 1.39, 95% CI [1.06-1.82]; P = 0.017). The incidence of arrhythmias and the median intubation time were both significantly lower in the GAE, compared with the GA, group (odds ratio = 0.41, 95% CI [0.22-0.78], P = 0.006 and hazard ratio = 1.73, 95% CI [1.31-2.27], P < 0.001, respectively). Patients in the GAE group were more likely to need vasoconstrictors intraoperatively than in the GA group (odds ratio = 2.50, 95% CI [1.22-5.12]; P = 0.012). The GAE, compared with GA, group reported significantly lower levels of impairment for all pain domains and reduced morphine usage (odds ratio = 0.07, 95% CI [0.03-0.17]; P < 0.001). Conclusion In patients undergoing off-pump coronary artery bypass surgery, the addition of thoracic epidural to general anesthesia significantly reduces the incidence of postoperative arrhythmias and improves pain control and overall quality of recovery, allowing earlier extubation and hospital discharge.