OBJECTIVE Despite recognized hemodynamic derangements during cardiac displacement, most patients appear to tolerate the off-pump procedure well. However, some patients unpredictably become hemodynamically unstable requiring emergency cardiopulmonary bypass or intra-aortic balloon pump support. After an experience of 5306 multivessel off-pump coronary artery bypasses (OPCABs), this study was undertaken to determine the factors that would identify the patients who were at a higher risk for the procedure. METHODS Prospective clinical investigation. METHODS Tertiary care academic cardiac care center. METHODS Five hundred consecutive patients undergoing multivessel OPCAB from September to December 2001. METHODS Various cardiac and extracardiac factors were charted in prespecified data-entry forms. Multiple logistic regression analysis was done to determine if any identifiable factors were predictors of a higher risk of unacceptable hemodynamic instability during OPCAB. Institution of IABP support or conversion to CPB were the endpoints of the study. RESULTS Of the 500 patients studied, significant hemodynamic instability developed in 24 (4.8%) patients. IABP support was instituted in 16 (3.2%) patients, and 8 (1.6%) were converted to CPB. Stepwise logistic regression identified ejection fraction <25% (p < 0.001), myocardial infarction of <1-month duration (p = 0.009), congestive heart failure (p = 0.016), and preoperative hemodynamic instability (p = 0.057) as predictors of conversion during OPCAB. CONCLUSIONS Patients with low left ventricular ejection fraction <25%, myocardial infarction of <1-month duration, congestive heart failure, or preoperative hemodynamic instability constitute the high-risk group for OPCAB.