Purpose: Internal herniation is a well-known complication of laparoscopic Roux-en-Y gastric bypass (L-RYGB). The aim of this study was to evaluate smoking as an independent risk factor for internal herniation after L-RYGB. Materials and Methods: This study was performed as an exploratory post hoc analysis of data from a previous published randomized controlled trial (RCT) designed to compare closure and non-closure of mesenteric defects in patients undergoing L-RYGB. The primary outcome of this study was to assess the significance of smoking as a risk factor for internal herniation after L-RYGB. Secondary outcome was early postoperative complications defined as Clavien-Dindo grade ≥ 2. Results: Four hundred one patients were available for post hoc analysis. The risk of internal herniation was significantly higher among patients who were smoking preoperatively (hazard ratio (HR) 2.4, 95% confidence interval (c.i.) 1.3 to 4.5; p = 0.005). This result persisted after adjusting for other patient characteristics (HR 2.2, 1.2 to 4.2; p = 0.016). 6.0% of the patients had postoperative complications within the first 30 days. 4.9% of these patients were smoking and 6.3% were not smoking, p = 0.657. 11.0% of the patients underwent surgery due to internal herniation by 5 years after the primary procedure. Conclusion: Smoking is a significant risk factor for internal herniation but did not increase risk for 30 days postoperative complications. Graphical Abstract: (Figure presented.)