Although a variety of technical and clinical problems of capsule endoscopy have been reported, their incidence and clinical importance are unknown. The objective was to evaluate the incidence and the type of such events. This was a retrospective analysis of 733 consecutive examinations at 4 large referral centers. The main outcome measurements were that the problems were classified as "technical," i.e., related to the functioning of the equipment, and "clinical," i.e., related to patient characteristics. For each type of event, the causes and the impact on the ability to reach a diagnosis were examined. A total of 183 problems were recorded in 174 patients (23.7%): one problem occurred in 165 patients, two in 9 patients. In 8.46% of patients, technical limitations or failures, or clinical complications prevented or hampered diagnosis. Technical problems (e.g., gaps in the recordings, short duration of capsule batteries, failure of downloading) occurred in the early phase of capsule use in 8.6% of examinations and prevented or hampered diagnosis in 2.9%. Clinical problems (difficulty/inability to swallow the capsule, incomplete small-bowel examination) occurred in 16.4% of examinations and hampered or prevented diagnosis in 6.4%. Capsule retention that required surgical or endoscopic retrieval occurred in 1.9% of cases. Technical problems were rare and hampered or prevented the diagnosis in a very small number of cases. The majority of clinical failures were related to an incomplete small-bowel examination.