Background Endocardial visualization is suboptimal by fundamental imaging in at least 30% of patients. Second harmonic imaging was developed for visualization of myocardial contrast agents. We have hypothesized that endocardial visualization may improve with harmonic imaging compared with fundamental imaging. Methods and results Accordingly, 40 consecutive patients with poor endocardial visualization by conventional echocardiography in at least 1 left ventricular segment (22-segment model) in the 4 standard views randomly underwent fundamental and harmonic imaging without contrast. The images were separately and randomly analyzed by 2 observers. Endocardial visualization was scored as 0, not visualized; 1, poorly visible; and 2, well visualized. Endocardial visualization indexes were also calculated. More segments were assigned a score of 0 (P < .001) and 1 (P < .001) by fundamental compared with harmonic imaging, whereas harmonic imaging demonstrated more segments with a score of 2 ( P < .001) compared with fundamental imaging. Endocardial visualization indexes were significantly better by harmonic imaging in the parasternal long axis (P < .005), short axis (P < .001), and apical 4- (P < .0001) and 2-chamber views (P < .0001). Similar results were obtained by a second observer. Agreement between the 2 observers regarding improvement, deterioration, or no change in score between harmonic and fundamental imaging was 88% (κ = 0.76). Interobserver and intraobserver agreements for systolic wall thickening scores also significantly improved with harmonic compared with fundamental imaging (P < .001). Conclusion Second harmonic imaging is superior to fundamental imaging for endocardial visualization in patients with suboptimal fundamental imaging. (Am Heart J 1999;138:163-8.)