Objective—To investigate whether administration of isoflurane prior to cardiopulmonary bypass (CPB) could partly account for the observed protection of the myocardial function and to decrease myocardial injury in patients undergoing coronary artery bypass grafting (CABG).Methods—Thirty‐four patients with stable angina who were scheduled for isolated elective CABG operations were randomized into the control group or isoflurane (ISO) group. In the ISO group, isoflurane was inhaled for 5 min followed by another 5‐min washout period before commencing CPB. The control group did not receive isoflurane. Hemodynamic data and biochemical markers of myocardial injury were measured perioperatively.Results—There were no adverse effects related to isoflurane. Cardiac index (CI) increased postoperatively as compared with the baseline. In the ISO group, there was a tendency for a greater increase of CI than that in the control group (p = 0.054, ANOVA for repeated measurements). At 1 h after CPB, the change of CI was much higher in the ISO group than that in the controls (p = 0.001). Both the creatine kinase cardiac isoenzyme (CK‐MB) and troponin I (TnI) reached peak value at 6 h after CPB. Isoflurane patients released slightly less CK‐MB than the controls postoperatively, but the difference was not significant (p = 0.16, ANOVA for repeated measurements). The release of TnI was similar in both groups (p = 0.65, ANOVA for repeated measurements).Conclusions—Administration of isoflurane prior to commencing CPB may bring an improvement in early hemodynamic performance after CABG operations.