Background <p>This study aimed to investigate the effects of adjuvant chemotherapy versus observation on recurrence and survival in patients treated with curative-intent resection for gallbladder cancer (GBC).</p> Methods <p>We selected consecutive GBC patients treated with curative-intent resection from a multicenter database between 2014 and 2021. The patients were subsequently divided into two groups: an observation group and a chemotherapy group. In the comparison analysis, propensity score matching was employed to adjust for potential confounding factors. The study endpoints were overall survival (OS) and progression-free survival (PFS). Event rates were estimated with Kaplan-Meier curves and compared via the log-rank test. The multivariable Cox regression model was used to identify factors independently associated with OS and PFS.</p> Results <p>A total of 604 GBC patients treated with curative-intent resection were included in this study, which were 511 in the observation group and 93 in the chemotherapy group. In the comparison between the chemotherapy group and the observation group, after propensity score matching, the 3-year OS rates and PFS rates were significantly higher in the chemotherapy group (<i>n</i> = 73) compared with the observation group (<i>n</i> = 188) after the 6 months. Among the 604 GBC patients, multivariable Cox regression analysis confirmed that chemotherapy was independently associated with better OS and PFS.</p> Conclusions <p>Adjuvant chemotherapy following curative-intent resection for GBC&#xa0;can reduce the risk of recurrence and prolong survival.</p>