Background Symptomatic cholelithiasis requiring treatment is a known side effect after Roux-en-Y gastric bypass (RYGB), but reported rates vary greatly. The objectives for this study were to evaluate the long-term frequency of surgical or endoscopic treatment for symptomatic cholelithiasis 10–15 years after RYGB and its relation to self-reported abdominal pain. Methods Observational data from 546 patients who underwent RYGB at public hospitals in Central Norway between March 2003 and December 2009 were analyzed. Results Median follow-up was 11.5 (range 9.1–16.8) years. Sixty-five (11.9%) patients had undergone cholecystectomy prior to RYGB. Out of the 481 patients with intact gallbladder, 77 (16.0%) patients underwent cholecystectomy and six (1.2%) patients had treatment for choledocholithiasis during the observation period. Median time from RYGB to cholecystectomy or treatment of choledocholithiasis was 51 (range 1–160) and 109 (range 10–151) months, respectively. Female sex was associated with an increased risk of subsequent cholecystectomy [OR (95% CI) 2.88 (1.31–7.15)], p < 0.05. There was a higher frequency of self-reported abdominal pain at follow-up [OR (95% CI) 1.92 (1.25–2.93)] among patients who underwent cholecystectomy before or after RYGB. Conclusion With a median follow-up of more than 11 years after RYGB, one in six patients with an intact gallbladder at time of RYGB underwent cholecystectomy, and 1.1% of the patients needed surgical or endoscopic treatment for choledocholithiasis. Patients with a history of cholecystectomy reported a higher frequency of abdominal pain.