Important risk factors for cardiovascular disease include excess dietary intake of saturated fat and (or) salt. This study tested the hypothesis that excess intakes of saturated fat (e.g., beef tallow) and salt cause greater myocardial cell death following ischemia–reperfusion injury than each risk factor alone. Male rats were divided into four groups: basal fat diet (4.5% as calories; control), high fat diet (40% as calories; FAT), basal fat diet and high salt (1% NaCl solution; SALT) and high fat diet and high salt (FATSALT). The gain in body weight was significantly higher for FAT and FATSALT groups than those of either the control or the SALT group. Five weeks of exposure to the dietary regimens did not significantly affect the coronary flow rate and except for the salt-fed group, had no effect on the rate–pressure–product of the isolated heart perfused in Langendorff mode. Although infarct size was not affected by the high fat diet, it was reduced by the high salt regimen relative to the high fat diet or the control groups. When rats were fed the FAT and SALT combination, the effect of salt feeding on infarct size was not observed. In addition, the FATSALT group displayed a more marked deterioration in contractile function following ischemia–reperfusion injury than the other groups. In conclusion, short-term intake of a high fat diet, which significantly increases body weight, does not worsen ischemia–reperfusion injury although the treatment prevents the reduction of infarct size associated with high salt feeding.