Background. 2,3-Butanedione monoxime (BDM) has been shown to possess cardioprotective properties related to the inhibition of cross-bridge force development, the reduction of myofilament Ca2+ sensitivity, and the attenuation of intracellular Ca2+ transients. This study tested the hypothesis that cardiac arrest achieved with BDM would be as effective as that achieved with St. Thomas' solution (StT). Methods. Isolated rabbit hearts, studied on a blood-perfused Langendorff column, underwent 1 hour of ischemia (37°C) and 30 minutes of reperfusion. Cardioplegia was administered every 20 minutes in the form of (1) Krebs-Henseleit solution only (control), (2) 20 mmol/L of BDM, or (3) StT. Recovery of developed pressure, atrioventricular activation times, and tissue water content were measured. Results. Recovery of developed pressure for the control, BDM, and StT groups was 44% ± 3% (p < 0.05 versus BDM and StT), 57% ± 5%, and 62% ± 4%, respectively. Atrioventricular activation times were significantly prolonged in the control group (42 ± 15 ms, p = 0.042) and the StT group (26 ± 9 ms, p = 0.034), but not in the BDM group (14 ± 8 ms). Tissue water content after reperfusion was 80% ± 0.4%, 80% ± 0.2%, and 76% ± 1.0% (p < 0.05 versus control) in the control, StT, and BDM groups, respectively. Conclusions. 2,3- Butanedione monoxime was as effective as StT in protecting the myocardium. Unlike StT, BDM ameliorated myocardial edema and atrioventricular conduction delay after reperfusion.