To investigate long-term re-bleeding events after a negative capsule endoscopy in patients with obscure gastrointestinal bleeding (OGIB) and the risk factors associated with the procedure. Patients referred to Hospital Egas Moniz (Lisboa, Portugal) between January 2006 and October 2012 with OGIB and a negative capsule endoscopy were retrospectively analyzed. The following study variables were included: demographic data, comorbidities, bleeding-related drug use, hemoglobin level, indication for capsule endoscopy, post procedure details, work-up and follow-up. Re-bleeding rates and associated factors were assessed using a Cox proportional hazard analysis. The Kaplan-Meier method was used to estimate the cumulative incidence of re-bleeding at 1, 3 and 5 years, and the differences between factors were evaluated. The study population consisted of 640 patients referred for OGIB investigation. Wireless capsule endoscopy was deemed negative in 113 patients (17.7%). A total of 64.6% of the population was female, and the median age was 69 years. The median follow-up was forty-eight months (interquartile range 24-60). Re-bleeding occurred in 27.4% of the cases. The median time to re-bleeding was fifteen months (interquartile range 2-33). In 22.6% (n = 7) of the population, small-bowel angiodysplasia was identified as the culprit lesion. A univariate analysis showed that age > 65 years old, chronic kidney disease, aortic stenosis, anticoagulant use and overt OGIB were risk factors for re-bleeding; however, on a multivariate analysis, there were no risk factors for re-bleeding. The cumulative risk of re-bleeding at 1, 3 and 5 years of follow-up was 12.9%, 25.6% and 31.5%, respectively. Patients who presented with overt OGIB tended to re-bleed sooner (median time for re-bleeding: 8.5 mo vs 22 mo). Patients with OGIB despite a negative capsule endoscopy have a significant re-bleeding risk; therefore, these patients require an extended follow-up strategy.