The sonographic Murphy sign, the presence of maximal tenderness elicited over a sonographically localized gallbladder, has been considered useful in the evaluation of patients with suspected acute cholecystitis. We prospectively evaluated this sign in 427 consecutive patients referred for evaluation of acute cholecystitis. The overall accuracy of the sonographic Murphy sign in the 219 patients with sufficient confirmation to be included in the statistical analysis was 87.2%. Sensitivity was 63% and specificity was 93.6%. The predictive value of a positive sign was 72.5%, while the predictive value of a negative sign was 90.5%. The sonographic Murphy sign is a useful, albeit imperfect, adjunct in the assessment of patients with suspected acute cholecystitis.