The efficacy of cold blood potassium cardioplegia during periods of aortic cross-clamping (greater than 100 minutes) was assessed in 127 patients undergoing a variety of open-heart surgical procedures at New York University Medical Center from january, 1978, to April, 1979. Ischemic intervals ranged from 100 to 267 minutes (mean, 128 minutes). Cardiac-related deaths occurred in only 3 patients (2.4%), and overall operative mortality was 8.7% (11 patients). The rate of perioperative infarction was 10%. Fourteen patients (11%) required vasopressor support or balloon counterpulsation after cardiopulmonary bypass despite the lengthy cross-clamp intervals. Multivariate analysis revealed no significant relationship between the length of cross-clamp time and operative mortality (p = 0.29), incidence of perioperative infarction (p = 0.54), or the occurrence of low-output syndrome postoperatively (p = 0.68). These findings suggest that cold blood potassium cardioplegia provides adequate myocardial protection when periods of arrest as long as 3 to 4 hours are required for complex cardiac surgical procedures.