Although the predictive and prognostic effect of primary tumor side in metastatic colorectal cancer is now widely accepted, it is poorly defined for early-stage disease. In the present analysis of > 6500 patients, we found stage-by-stage differences in survival outcomes according to the primary tumor location, which was partially attributable to differences in survival after recurrence. However, the primary tumor location did not influence the benefit of adjuvant chemotherapy. Background: Multiple studies have defined the prognostic and potential predictive significance of the primary tumor side in metastatic colorectal cancer (CRC). However, the currently available data for early-stage disease are limited and inconsistent. Materials and Methods: We explored the clinicopathologic, treatment, and outcome data from a multisite Australian CRC registry from 2003 to 2016. Tumors at and distal to the splenic flexure were considered a left primary (LP). Results: For the 6547 patients identified, the median age at diagnosis was 69 years, 55% were men, and most (63%) had a LP. Comparing the outcomes for right primary (RP) versus LP, time-to-recurrence was similar for stage I and III disease, but longer for those with a stage II RP (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.52-0.90; P <.01). Adjuvant chemotherapy provided a consistent benefit in stage III disease, regardless of the tumor side. Overall survival (OS) was similar for those with stage I and II disease between LP and RP patients; however, those with stage III RP disease had poorer OS (HR, 1.30; 95% CI, 1.04-1.62; P <.05) and cancer-specific survival (HR, 1.55; 95% CI, 1.19-2.03; P <.01). Patients with stage IV RP, whether de novo metastatic (HR, 1.15; 95% CI, 0.95-1.39) or relapsed post–early-stage disease (HR, 1.35; 95% CI, 1.11-1.65; P <.01), had poorer OS. Conclusion: In early-stage CRC, the association of tumor side and effect on the time-to-recurrence and OS varies by stage. In stage III patients with an RP, poorer OS and cancer-specific survival outcomes are, in part, driven by inferior survival after recurrence, and tumor side did not influence adjuvant chemotherapy benefit.