The effects of left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT) on LV remodeling and dyssynchrony are not well defined. Sixty-one patients (age 60 ± 11 years, 76% men) were evaluated by echocardiography before and 4 ± 2 months after CRT and grouped by the LV lead placement (lateral, posterolateral, or anterolateral). Echocardiographic measurements included LV volumes and LV ejection fraction. Tissue Doppler imaging was used to assess for inter- and intraventricular systolic and diastolic dyssynchrony. Analysis of variance was used to determine the effect of the LV lead placement on echocardiographic variables after CRT. The LV lead was placed in a lateral cardiac vein in 33 patients (54%), posterolateral in 15 (25%), and anterior in 13 (21%). Lateral LV lead placement was associated with significantly smaller LV volumes compared with the posterolateral lead placement (p <0.01). Diastolic dyssynchrony improved significantly with lateral lead placement compared with the anterior lead location (p <0.05). Improvement in LV ejection fraction and inter- and intraventricular systolic dyssynchrony was similar among the 3 groups. In conclusion, in patients undergoing CRT, a lateral lead location resulted in greater reverse LV remodeling and improved diastolic dyssynchrony compared with other lead placement locations.