BACKGROUND: Due to conflicting study results on the effect of laterality on overall survival in primary colon cancers, we sought to examine the impact of left compared to right-sided primary tumors on overall survival for stage I-III colon cancer using the largest dataset to date. METHODS: The 2006-2013 NCDB was queried for patients with single primary, stage I-III colon adenocarcinoma and grouped by stage and tumor location. RESULTS: For stage I-II tumors, 114,839 patients had resection (62% right:38% left). After adjustment, patients with right-sided tumors had superior survival ([HR right as reference]: 1.13, 95% CI 1.09-1.17, p < 0.001). For stage III tumors, 71,024 patients had resection, (59% right:41% left). After adjustment, patients with left-sided tumors had superior survival with chemotherapy (HR 0.85, p < 0.001) and no difference in survival without chemotherapy (HR 0.97, p = 0.18). CONCLUSIONS: The side of the primary tumor impacts overall survival across stages for colon adenocarcinoma. Patients with right-sided tumors have superior survival for stage I-II disease while patients with left-sided stage III disease demonstrate a survival advantage, suggesting an opportunity for investigators to use sidedness as a surrogate for prognosis and chemoresponsiveness.