Purpose: Risk factors of Gallbladder Cancer (GBC) are not well-defined resulting in greater than 60% of GBCs being diagnosed incidentally following cholecystectomy performed for presumed benign indications. As most localized GBC require more extensive oncologic surgery beyond cholecystectomy, this study aims to examine factors associated with incidentally found GBC to improve preoperative and intraoperative diagnosis. Methods: The American College of Surgeons National Surgical Quality Improvement Program Database from 2007-2017 was used to identify cholecystectomies performed with and without a final diagnosis of GBC. Univariate and multivariable logistic regression were used to compare demographic, intraoperative, and postoperative characteristics among those with and without a diagnosis of GBC. Results: The incidence of GBC was observed to be 0.11% (441/403,443). Preoperative factors associated with risk of GBC included age >60 (OR 6.51, p<.001), female sex (OR 1.75, p<.001), history of weight loss (2.58, p<.001), and elevated preoperative alkaline phosphatase level (OR 1.67, p=.001). Open approach was associated with 7 times increased risk of GBC compared to laparoscopic approach (OR 7.33, p<.001). In addition to preoperative factors and surgical approach, longer mean operative times (127 minutes vs 70.7 minutes, p<.001) were significantly associated with increased risk of GBC compared to benign final pathology. Conclusion: This study demonstrates that those with incidentally discovered GBC at cholecystectomy are unique from those undergoing cholecystectomy for benign indications. By identifying predictors of GBC, surgeons can choose high risk individuals for pre-operative oncologic evaluation and consider better tools for identifying GBC such as intraoperative frozen pathology.

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