Background Fast-track cardiac surgery is an important global concern as it can decrease the duration of ICU stay, duration of hospitalization, and total cost of cardiac surgery. The greater the success in fast-track cardiac surgery, the greater the survival rate as there will be fewer cancellations due to unavailability of beds. Objective Our aim is to assess the impact of thoracic epidural dexmedetomidine-bupivacaine on the hemodynamics and analgesic profile, and thus in fast-tracking surgery in patients subjected to off-pump coronary artery bypass grafts (CABG). Patients and methods Fifty-six patients of either sex, aged 50–70 years, subjected to off-pump CABG were randomly assigned to two groups: a control group receiving general anesthesia (GA); and an epidural general group receiving GA combined with thoracic epidural dexmedetomidine 1 μg/kg with 8 ml 0.25% bupivacaine and top-up doses of 2 ml. Bupivacaine 0.25% was given hourly during the operation until closure of the sternum. Perioperative hemodynamics (heart rate, mean arterial pressure, and central venous pressure) and PaCO2, PaO2, and pH were recorded at the following intervals: at baseline, before skin incision, before sternotomy, after sternal closure, and in the ICU. Time to awakening and time to extubation were recorded. Also, analgesics and vasoactive and vasodilator medications were recorded. Pain assessment was made using the visual analogue scale on a scale of 0–10. Total duration of stay in ICU and hospital stay was recorded. Results Postoperative heart rate and mean arterial pressure were significantly lower in the epidural group when compared with the control group. Time to first awakening and extubation was also significantly earlier in the epidural group than in the control group. Total intraoperative fentanyl dose (μg/kg) was less in the epidural group than in the general group, and postoperative morphine requirements (mg/kg) were significantly lower in the epidural group than in the control group. There was lesser need for cardiovasoactive drugs (β-blockers, inotropes) and vasodilators in the epidural group compared with the control group. Visual analogue scale revealed better analgesic profile at the time of extubation in the epidural group. Total ICU and hospital stay was significantly shorter in the epidural group than in the control group. Conclusion GA supplemented with thoracic epidural dexmedetomidine with bupivacaine in off-pump CABG resulted in more perioperative hemodynamic stability, earlier extubation, lower pain score, and less analgesics, vasoactive and vasodilator drug requirements compared with GA alone. Successful fast tracking of cardiac surgery in off-pump CABG can be achieved using this anesthetic technique.