Ginsenoside Rb3 (G‑Rb3) has been demonstrated to alleviate myocardial ischemia reperfusion injury (MIRI); however, it is difficult to separate G‑Rb2 from its isomer G‑Rb3. The current study aimed to compare the cardioprotective effects of G‑Rb3 and the concomitant use of G‑Rb3 and G‑Rb2 (G‑Rb3/Rb2) on MIRI in rats. A rat model of MIRI was established by ligation of the left anterior descending coronary artery and the rats were randomly divided into five groups. Prior to MIRI, G‑Rb3/Rb2 (20 mg/kg), G‑Rb3 (20 mg/kg) and diltiazem (DLZ; 20 mg/kg, as a positive control) were orally administered to the rats once a day for 3 consecutive days. After 30 min of ischemia and 120 min of reperfusion, cardiac function, infarct size, cardiac marker enzymes, antioxidative parameters, inflammatory factors, histopathological changes, cardiomyocyte apoptosis, and B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein and caspase‑3 expression were determined using a multi‑channel physiological recording system, nitrotetrazolium blue chloride, biochemical kits, radioimmunoassay kits, hematoxylin and eosin, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, immunohistochemistry and reverse transcription‑quantitative PCR, respectively. The results indicated that treatment with G‑Rb3/Rb2 significantly protected rats against MIRI, as shown by improved cardiac function, reduced myocardial ischemic area, decreased serum activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase MB, decreased serum concentrations of interleukin‑6 and tumor necrosis factor‑α, decreased malondialdehyde concentration in myocardial tissues, increased activities of superoxide dismutase, glutathione peroxidase and catalase in myocardial tissues, reduced histopathological changes in myocardial tissues, reduced number of apoptotic cardiomyocytes, and changes in the expression levels of caspase‑3, Bcl‑2 and Bax. In addition, the effects of treatment with G‑Rb3/Rb2, G‑Rb3 or DLZ were equivalent. The protective effects of G‑Rb3/Rb2 on MIRI were similar to those of G‑Rb3 in terms of oxidative stress, inflammatory factors and inhibition of cardiomyocyte apoptosis. Therefore, G‑Rb3/Rb2 may be developed as a concomitant treatment for MIRI.