The effects of acute excessive alcohol ingestion on echocardiographic parameters of left ventricular (LV) function are unclear. One hundred ninety-nine healthy subjects (44 ± 5 years, 71% male) were prospectively examined within 6 hours after excessive alcohol ingestion as well as after 4 weeks with strict alcohol abstinence. Echocardiography was performed at baseline and follow-up for conventional parameters (left ventricular ejection fraction LVEF, transmitral E and A Doppler flow velocities, E/A ratio, tissue Doppler velocity lateral and septal (é), E/é ratio, deceleration time of E, and isovolumic relaxation time) and myocardial deformation data (such as global radial and global and layer-specific circumferential endo and epi global CS and longitudinal endo and epi global LS strain). Multivariate regression was used to assess the impact of independent variables on echocardiographic parameters. Alcohol levels were 1.2 ± 0.3 g/L at the time of drinking cessation. After alcohol ingestion endo CS (30% ± 2% vs 37% ± 3%, P = .008) and endo LS (27% ± 4% vs 33% ± 3%, P = .002) were significantly lower at baseline versus follow-up. Blood pressure, LVEF and heart rate, and other echocardiographic parameters did not differ between the two examinations. Alcohol levels were modestly, negatively associated with change in endo CS and endo LS (r = -0.54, 95% CI, -0.63 to -0.43, P < .001; and r = -0.26, 95% CI, -0.39 to -0.14; P < .003, respectively). Alcohol levels were the strongest predictor for endo CS (β = -4.84; 95% CI, -6.31 to -3.37) and endo LS (β = -2.50; 95% CI, -4.32 to -0.68). Acute alcohol ingestion effects endocardial CS and LS, suggesting an acute and transient toxic effect on myocardial deformation, an effect that remains undetected by conventional echocardiographic parameters. The current findings may help clinicians to gain more understanding into the mechanism of developing an alcohol cardiomyopathy and to detect early persistent alcohol-induced myocardial disturbances for an effective therapy in time to prevent harm.