Whether coronary artery bypass grafting (CABG) should be performed on- or off-pump remains a matter of debate. We aim to present our experience with off-pump CABG. Early clinical outcome and adverse events were analyzed over the time course of the study. Methods: A total of 4310 patients undergoing isolated off- pump CABG from January 2002 until December 2016 at the Malabar Institute of Medical Sciences in India were included. Preoperative, intraoperative, and postoperative, as well as follow-up data were prospectively collected. To analyze the differences of patient characteristics and outcomes over time, five-year periods were created (early: 2002-2006; middle: 2007-2011; late: 2012-2016). Traditional techniques of quality control monitoring were applied. Results: The mean age of our patients was 59 ± 9 years, and 13% (533) were female. Postoperative mortality was observed in 0.7% (25), acute renal failure and stroke in 0.2% (8) each, and mediastinitis in 1.2% (53) of the patients. Despite the progressive worsening of the patient risk profile, significant improvement in mortality was observed over time, while stroke, acute renal failure, and mediastinitis remained similar. Continuous quality control monitoring revealed that the system was within the control boundaries for the entire period of the study. The current probability of 30-day mortality or conversion to on-pump CABG is about 0.5%. Conclusion: Off-pump CABG is safe and effective for patients undergoing CABG. It can provide superior results compared to on-pump CABG, particularly when performed by a dedicated off-pump surgeon.