Abstract Background Because hearts in acute myocardial infarction are often prone to ischemia-reperfusion damage during cardiac surgery, we investigated the influence of intracellular crystalloid cardioplegia solution (CCP) and extracellular blood cardioplegia solution (BCP) on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction. Methods Following euthanasia, the hearts of 50 rats were quickly excised, cannulated, and inserted into a blood-perfused isolated heart apparatus. A regional myocardial infarction was created in the infarction group (18 hearts) for 120 min; the control group (32 hearts) was not subjected to infarction. In each group, either Buckberg BCP or Bretschneider CCP was administered for an aortic clamping time of 90 min. Functional parameters were recorded during reperfusion: coronary blood flow, left ventricular developed pressure (LVDP) and contractility (dp/dt max). Infarct size was determined by planimetry. The results were compared between the groups using analysis of variance or parametric tests, as appropriate. Results Cardiac function after acute myocardial infarction, 90 min of cardioplegic arrest, and 90 min of reperfusion was better preserved with Buckberg BCP than with Bretschneider CCP relative to baseline (BL) values (LVDP 54 ± 11% vs. 9 ± 2.9% [p = 0.0062]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]), whereas coronary flow was similarly impaired (BCP 55 ± 15%, CCP 63 ± 17% [p = 0.99]). The infarct in BCP-treated hearts was smaller (25% of myocardium) and limited to the area of coronary artery ligation, whereas in CCP hearts the infarct was larger (48% of myocardium; p = 0.029) and myocardial necrosis was distributed unevenly to the left ventricular wall. Conclusions In a rat model of acute myocardial infarction followed by cardioplegic arrest, application of BCP leads to better myocardial recovery than CCP.