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Background Wireless capsule endoscopy has become the gold standard for the examination of small bowel. However, its role in the evaluation of patients suffering from chronic abdominal pain is not yet clearly defined. We conducted an open-label prospective multi-center study to evaluate the yield and clinical outcome of capsule endoscopy in patients with chronic abdominal pain with/without diarrhea. Methods Seventy-two patients with chronic (> 3 months) abdominal pain with/without diarrhea in whom the underlying pathology could not be diagnosed by conventional modalities, underwent capsule endoscopy in either of the 6 participating centers. Patients were then followed up for clinical outcomes. Results The overall diagnostic yield of capsule endoscopy was 44.4%. More specifically, its diagnostic yield was 21.4% in patients with abdominal pain and negative inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), 66.7% in patients with abdominal pain and positive inflammatory markers, 0% in patients with abdominal pain, diarrhea and negative inflammatory markers, and 90.1% in patients with abdominal pain, diarrhea and positive inflammatory markers. Both univariate and multivariate regression analyses showed that abnormal C-reactive protein and erythrocyte sedimentation rate were significant factors related with positive capsule endoscopy findings. Conclusions Chronic abdominal pain with/without diarrhea should be accompanied by elevated inflammatory markers to be regarded as a valid indication for capsule endoscopy. The yield of capsule endoscopy in such patients is reasonably high and clinical outcomes of patients treated with capsule endoscopy findings as a guide are significant.