<h3>Background</h3> Ischemic heart disease (IHD) is associated with decreased cardiac conduction, providing a substrate for reentrant arrhythmia and sudden cardiac death. Connexin43 (Cx43) is the principal gap junction protein responsible for allowing current to pass through cardiomyocytes in the ventricles. Cx43 expression is known to be reduced in the left ventricle following IHD. Recently, we showed that ROS stimulates c-Src phosphorylation (p-Src), allowing p-Src binding to the scaffolding protein zonula occludens-1 (ZO-1) and destabilizing Cx43, leading to Cx43 lateralization and degradation. We tested whether Src inhibition would prevent Cx43 degradation in IHD. <h3>Methods</h3> Coronary artery occlusion was performed on 12-week-old mice causing myocardial infarction (MI). MI mice were treated with PP1, a p-Src inhibitor, or PP3, an inactive analogue. PP1, PP3, and sham hearts were compared functionally by echocardiography, optical mapping, ECG telemetry analysis, and arrhythmia inducibility by ventricular pacing. Tissues were collected for immunohistochemistry and Western blot analysis. <h3>Results</h3> Scar borders of PP1 groups demonstrated restored conduction velocity compared with PP3-treated mice (PP1 = 33 cm/s, PP3=18 cm/s). In PP1-treated mice, there was a 60 % decrease in p-Src activation and a 25% increase in Cx43 expression at the scar border compared with PP3 groups. PP1 did not change infarct size, ECG pattern, or cardiac function (ejection fraction: sham=61 ± 1, PP1=39 ± 2, PP3=39 ± 2). <h3>Conclusions</h3> Src inhibition improves Cx43 levels and conduction velocity after MI. Src inhibitors may represent a new class of antiarrhythmic compounds.