Cardiopulmonary bypass (CPB) has been suggested to be a cause of complex systemic inflammatory response that significantly contributes to several adverse postoperative complications. In the last few years, off-pump coronary artery bypass grafting (OPCAB) has gained widespread attention as an alternative technique to conventional on-pump coronary artery bypass grafting (ONCAB). However, a degree of uncertainty regarding the relative merits of ONCAB and OPCAB continues to be a significant issue. Surgeons supporting off-pump surgery, state that the avoidance of the CPB leads to significantly reduced myocardial ischemia-reperfusion injury, postoperative systemic inflammatory response and other biological derangements, a feature that may improve the clinical outcomes. However, perfection in perioperative care, surgical technique and methods of attenuating the untoward effects of CPB has resulted in better clinical outcome of ONCAB as well. Possible reasons of these controversial opinions are that high-quality studies have not comprehensively examined relevant patient outcomes and have enrolled a limited range of patients. Some studies may have been too small to detect clinically important differences in patient outcomes between these two modalities. We present a review of the available scientific interpretation of the literature on OPCAB with regard to safety, hemodynamic changes, inflammation, myocardial preservation and oxidative stress. We also sought to determine from different reported retrospective and randomized control studies, the initial and the long-term benefits of this approach, despite the substantial learning curve associated with OPCAB.