OBJECTIVE: Because of the reported association between intussusception and a rotavirus vaccine, future clinical trials of rotavirus vaccines will need to include intussusception surveillance in the evaluation of vaccine safety. The aim of this study is to develop and validate a clinical case definition for the diagnosis of acute intussusception. METHODS: A clinical case definition for the diagnosis of acute intussusception was developed by analysis of an extensive literature review that defined the clinical presentation of intussusception in 70 developed and developing countries. The clinical case definition was then assessed for sensitivity and specificity using a retrospective chart review of hospital admissions. Sensitivity of the clinical case definition was assessed in children diagnosed with intussusception over a 6.5-year period. Specificity was assessed in patients aged <2 years admitted with bowel obstruction and in patients aged <19 years presenting with symptoms that may occur in intussusception. RESULTS: The clinical case definition accurately identified 185 of 191 assessable cases as "probable" intussusception and six cases as "possible" intussusception (sensitivity, 97%). No case of radiologic or surgically proven intussusception failed to be identified by the clinical case definition. The specificity of the definition in correctly identifying patients who did not have intussusception ranged from 87% to 91%. CONCLUSIONS: The clinical case definition for intussusception may assist in the prompt identification of patients with intussusception and may provide an important tool for the future trials of enteric vaccines.