BACKGROUND Warm heart surgery implies continuous perfusion with normothermic blood cardioplegia. Interruption of cardioplegia, however, facilitates construction of distal coronary anastomoses and is the method practiced by many surgeons. To determine whether intermittency is harmful, we present results from 720 coronary bypass patients, protected with intermittent antegrade warm blood cardioplegia, that were derived from a previous study of normothermic versus hypothermic cardioplegia. RESULTS Mean +/- SD age was 60.8 +/- 9.0 years; 27% of cases were urgent; 16% of patients had > 50% left main stenosis, and 19% had grade III or IV ventricles. A mean of 3.2 +/- 0.9 grafts was constructed. The average aortic cross-clamp time was 61.8 +/- 22.2 minutes. The longest single time off cardioplegia (LTOC) averaged 11.4 +/- 4.0 minutes per patient. The cumulative time off cardioplegia as a percentage of the cross-clamp time (PTOC) was 48.2 +/- 18.6% per patient. LTOC and PTOC were divided into quartiles (LTOC, < 10, 10 to 11, 12 to 13, and > 13 minutes; PTOC, < 36%, 36% to 49%, 50% to 62%, and > 62%) and related to the prespecified composite outcome of mortality, myocardial infarction according to serial CK-MB sampling, and low-output syndrome (LOS). Longer LTOC was harmful (event rates per quartile, 13.5%, 10.3%, 10.9%, and 19.0%; P = .046), whereas longer PTOC was protective (16.1%, 17.2%, 9.4%, and 10.6%; P = .07). Stepwise logistic regression was performed, controlling for demographic and angiographic predictors. In the multivariate models, LTOC remained detrimental (P = .07) and PTOC remained beneficial (P = .053). Additional modeling after entering surgeon identity (P < .001) into the risk equation eliminated the PTOC effect, whereas LTOC remained predictive of adverse outcomes (P = .053; odds ratio, 1.06; 95% CI, 1.00, 1.13). CONCLUSIONS The data indicate that a reasonable margin of safety exists with intermittent, antegrade warm blood cardioplegia. Repeated interruptions of warm blood cardioplegia are unlikely to lead to adverse clinical results if single interruptions are < or = 13 minutes.