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Background: Residual disease (RD) has been described as one of the most relevant prognostic factors after radical surgical resection for incidental gallbladder cancer (IGC). The purpose of the present study was to analyze patterns of RD and determinant prognostic factors in patients undergoing re-resection for IGC., Methods: Patients undergoing re-exploration due to IGC between 1990 and 2014 were identified in two referral centers from different South-American countries. Patients submitted to a radical definitive operation were included in the study. Demographics and tumor-treated related variables were analyzed in correlation with RD and survival. The site of RD, local (gallbladder bed) or regional (lymph nodes and bile duct) was correlated with disease-specific survival (DSS)., Results: Of 265 patients with IGC submitted to surgery, 168 underwent a radical re-resection and RD was found in 58 (34.5%). Demographic, clinical and surgical variables were compared between both centers showing differences in type of resection, laparoscopic approach, T stages and disease stage. Location of RD was regional in 34 (20.2%) and local in 24 (14.3%), and no residual disease was found in 110 (65.5%) patients. T stage (T1b = 20%, T2 = 23.8%, T3 = 71.7%, p < 0.001) and disease stage (p < 0.001) were independent predictors of RD. Finding RD at any location reduced the DSS in comparison with non-RD patients (19.6 months vs. 62.7 months p < 0.001). No differences in DSS according to the location of RD were found, and all anatomic sites were equally poor (p = 0.27). RD at any site predicted DSS (p < 0.001), independently of all other IGC variables., Conclusions: IGC presented similar clinical parameters in two different countries of South America. RD was demonstrated as the most critical prognostic variable in patients with IGC treated by a radical resection. The presence of RD was associated with poor outcome, independently of any anatomic location. Future studies incorporating neoadjuvant chemotherapy in the treatment of patients with prognostic factors for RD are required to improve survival in this entity.