Objective: Ischemic pre-conditioning (IPreC) and post-conditioning (IPostC) protect the human myocardium against ischemia/reoxygenation (I/R) injury. However, the two interventions may induce variable degrees of protection, suggesting different mechanisms of action. This study assessed whether IPreC and IPostC confer greater protection when used in combination rather than individually. Methods: The right atrial appendages from 50 patients were subjected to 90 min of ischemia and 120 min of reoxygenation according to different protocols: IPostC (1 cycle of 120 and 180 sec of I/R) and IPreC (1 cycle of 5 min ischemia/5 min reoxygenation), alone and in combination. Lactate dehydrogenase (LDH) release was measured as an index of tissue injury and 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction as an index of cell viability. Results: The results showed that in one half of muscles the combined use of IPreC and IPostC reduced injury compared to either intervention alone whereas in the remaining half the combined approach had no greater effect. Nonetheless, the addition of IPreC to IPostC increased the number of protected samples by almost 20% compared to IPostC alone. Conclusion: The results demonstrate the lack of a uniform response to IPreC and IPostC and that the combined use of the two treatments improves protection although does not abolish the further myocardial injury that occurs in some instances in response to IPostC.