Background: While gender has been shown to be a predictive and prognostic factor in certain cancers, data for colon cancer (CC) are conflicting, with prior studies mainly focusing on 5-fluorouracil (5-FU) alone. To clarify the influence of gender on CC outcomes, our aims were to 1) compare outcomes between men and women in a large cohort of patients (pts) with early stage disease and 2) describe whether the effect of gender varies based on age, stage, time period and type of adjuvant therapy received. Methods: A pooled, retrospective analysis of individual data from 33,345 CC pts enrolled in 24 trials of various adjuvant systemic therapies was conducted. Chemotherapy consisted of 1) 5-FU, 2) 5-FU variations, 3) oxaliplatin, 4) irinotecan, or 5) oral-based regimens. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and time to recurrence (TTR). Cox proportional hazard models and interaction analyses were used to explore the effect of gender on outcomes. Results: We included 18,245 men and 15,100 women. Baseline characteristics were comparable between genders: median age was 61 years; 91% were White; 31% and 69% had stage II and III disease, respectively, in the entire cohort. Overall, men had inferior prognoses when compared to women for all endpoints, even after adjusting for age, stage and treatment (Table). Gender was not a predictive factor of treatment efficacy (interaction p for gender and treatment = 0.39, 0.61 and 0.78 for DFS, OS and TTR, respectively). In exploratory analyses, worse outcomes in men were more prominent in the older subset (HR 1.08 in age≤65 vs. 1.19 in age>65, interaction p=0.006 for DFS and HR 1.11 in age≤65 vs. 1.19 in age>65, interaction p=0.02 for OS). Stage of disease, study time period and type of adjuvant regimen did not modify the prognostic value of gender. Conclusions: Gender is a modest independent prognostic marker in early stage CC, particularly in older pts.