Background: The goal of this study was to determine the impact of mesenteric defect closure and Roux limb position on the rate of internal hernia after laparoscopic Roux-en-Y gastric bypass (LRYGB). Methods: A retrospective review was conducted of all LRYGB patients from 2001 to 2011 who had all internal hernia (IH) defects closed (DC) or all defects not closed (DnC). Results: Of 914 patients, 663 (72.5 %) had DC vs. 251 (27.5 %) with DnC, and 679 (74.3 %) had an ante-colic vs. 235 (25.7 %) with a retro-colic Roux limb. Forty-six patients (5 %) developed a symptomatic IH. Of these, 25 (3.8 %) were in the DC vs. 21 (8.4 %) in the DnC group (p = 0.005), and 26 (3.8 %) were in the ante-colic vs. 20 (8.5 %) in the retro-colic Roux limb position (p = 0.005). Data from 45 patients were available for further analysis. The most common symptom was chronic postprandial abdominal pain (53.4 %). All patients underwent CT scan consistent with IH in 26 patients (57.5 %), suggestive in 7 (15.6 %), showing small bowel obstruction in 4 (8.9 %), and negative in 8 (17.8 %). Conclusions: Closure of mesenteric defects and ante-colic Roux limb position result in a significantly lower IH rate. Furthermore, a high index of suspicion must be maintained since symptoms may be nonspecific and imaging may be negative in nearly 20 % of patients. © 2013 The Society for Surgery of the Alimentary Tract.