After the ingestion of iso-osmolar polyethylene glycol solution, the small bowel can be visualized on ultrasonography. The aim of this study was to assess sensitivity and specificity of SICUS in diagnosis of small bowel lesions. A total of 53 consecutive patients with suspected intestinal pathology underwent a diagnostic workup, including a small bowel follow-through and SICUS performed by independent operators. The sonologist was unaware of the clinical data. Diagnostic sensitivity and specificity were assessed using radiologic findings. Diagnostic sensitivity of SICUS was 100%, with a specificity of 97%. The concordance index was 0.956 (p < 0.003, kappa statistics) and the conformity between SICUS and radiology was 1. The diagnostic accuracy of SICUS to detect small bowel lesions is comparable to that of small bowel follow-through. Results of this study support the use of noninvasive, widely available, inexpensive, and nondemanding SICUS as an initial investigation in patients with suspected small bowel disease.