Objective: Most coronary artery bypass grafts are done by applying cardiopulmonary bypass, which usually induces unwanted inflammatory reactions and impairs the outcomes. In order to minimize the perilous response of cardiopulmonary bypass, pentoxifylline was getting used orally. Methods: In a prospective, placebo-controlled, randomized clinical trial, 178 coronary artery bypass graft candidates with ejection fraction lower/equal to 30%, divided into two equal groups (pentoxifylline and control), participated in the study. Pentoxifylline patients received 400 mg pentoxifylline 3 times a day for 3 days before operation. The outcomes were compared between groups using student’s t-test, Mann-Whitney U-test, Pearson chi-square, or Fisher’s exact test. Results: Pentoxifylline administration did not significantly affect troponin-T (p=0.68), but it reduced tumor necrosis factor-α (p=0.01) and interleukin-6 (p=0.01). It improved left ventricular ejection fraction significantly (p=0.01). White blood cell and platelet counts, hemoglobin, and hematocrit were not influenced by pentoxifylline. The drug did not affect blood urea nitrogen and creatinine, occurrence of renal failure, cerebrovascular accidents, and in-hospital mortality rate. The need for an intra-aortic balloon pump, cardiopulmonary bypass, and aortic cross-clamp times were not affected, either. Pentoxifylline decreased the intensive care unit stay (p<0.001), ventilation time, 10.4 hours in the pentoxifylline group against 14.7 hours in the control group (p=0.01), and the requirement of inotropic agents (p=0.02) and blood transfusion (p=0.01). Conclusion: Pentoxifylline has more beneficial potencies in reducing adverse events after coronary artery bypass graft using cardiopulmonary bypass, than what are known.