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Background: Ischemic contracture compromises hemodynamic effectiveness of cardiopulmonary resuscitaton (CPR) and resuscitability. 2,3-Butanedione monoxime (BDM) reduced ischemic contracture by inhibiting actin-myosin cross-bridge formation in an isolated heart model. We investigated the effects of BDM on ischemic contracture and resuscitation outcomes in a pig model of out-of-hospital cardiac arrest (OHCA). Methods: After 15 min of untreated ventricular fibrillation followed by 8 min of basic life support, sixteen pigs were randomized to receive either 2 ml·kg -1 of BDM solution (25 g·l -1 ) (BDM group) or 2 ml·kg -1 of saline (control group) during advanced cardiac life support (ACLS). ACLS was continued until restoration of spontaneous circulation (ROSC) or until 12 min had lapsed since the start of ACLS. To obtain a long axis view of left ventricle (LV) using a transesophageal echocardiography (TEE) probe during CPR, a skin incision was made to the right of the xiphoid process and a pocket extending 4-5 cm under the sternum was made to ensure a free passage of the TEE probe. The primary outcome was ROSC and the secondary outcomes were LV wall thickness and chamber area. Results: There was a trend toward a higher rate of ROSC in the BDM group (8 of 8 versus 4 of 8, p = 0.077). During the ACLS, the control group showed an increase in LV wall thickness from 10.0 cm (10.0-10.8) to 13.0 cm (13.0-13.0) and a decrease in LV chamber area from 8.13 cm 2 (7.59-9.29) to 7.47 cm 2 (5.84-8.43). In contrast, the BDM group showed a decrease in the LV wall thickness from 10 cm (9.0-10.8) to 8.5 cm (7.0-9.8) and an increase in the LV chamber area from 9.86 cm 2 (7.22-12.39) to 12.15 cm 2 (8.02-14.40). Mixed model analyses on LV wall thickness and LV chamber area revealed significant effects for group and significant group-time interactions. Conclusions: BDM administered during cardiopulmonary resuscitation reversed ischemic contracture and tended to improve the resuscitability in a pig model of OHCA.