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Patients with spinal cord injury (SCI) have an increased prevalence of cholelithiasis. The goal of this study was to clarify the presentation and management of symptomatic gallstone disease in patients with SCI. We performed a retrospective study of presentation of gallstone complications in patients with SCI who underwent cholecystectomy for complications of gallstone disease. The West Roxbury Veterans Administration Medical Center SCI registry (605 patients) was searched for patients who had undergone cholecystectomy more than 1 year after SCI (35 patients). Gallbladder disease profiles for the 35 patients undergoing cholecystectomy for complications of gallstone disease were prepared, including demographics, clinical presentation, diagnostic studies, operative and pathologic findings, and postoperative complications. All patients were white. Thirty-four were male and the mean age was 50 years (range 35 to 65 years). The majority of patients (66%) complained of right upper quadrant abdominal pain, even those patients with SCI at high (i.e., cervical) levels. Of the 35 patients in our study group, 22 (63%) had biliary colic and chronic cholecystitis, nine (26%) had acute cholecystitis (gangrenous cholecystitis in two), two (6%) had choledocholithiasis symptoms or cholangitis, and two (6%) had gallstone pancreatitis. Major perioperative morbidity occurred in two (6%) of the 35 patients (pulmonary embolus; intraoperative hemorrhage), and there were no deaths. In the great majority of patients with SCI, cholelithiasis presents with chronic pain and not with life-threatening complications. Our findings suggest that presentation is no more acute in patients with SCI than in the general population. Characteristic symptoms and signs are not necessarily obscured by SCI injury, regardless of the level.