Background: Microsatellite instability high (MSI-H) status indicates better prognosis in early stage colon cancer (CC) compared to microsatellite stable (MSS). However, the impact of tumor side, left side (L) versus right side (R), is not described on clinical outcomes based on MSI status. Methods: Patients with pathological stage II and III primary adenocarcinoma of the colon between 2010 and 2015 were identified in the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490 and C18.0, 18.2,18.3, 18.5,18.6, 18.7. Univariate (UVA) and multivariable (MVA) survival analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on tumor location and treatment received with Log-rank test. Results: A total of 35,071 patients with stage II (n = 17,629) and III (n = 17,442) CC were identified. 51.3% female; 81.5% Caucasian; median age 66 (range, 18-90). Majority of stage II and III tumors were R, 61.2% (n = 10,794) and 56.0% (n = 9,763). MSI-H was more common in stage II compared to III, 23.3% (n = 4,115) vs 18.2% (n = 3,171) (p < 0.0001). Survival was better in stage II MSI-H compared to MSS, 5 year-OS 75.1% vs 71.8% (p = 0.0057). However, stage III CC survival was better in MSS compared to MSI-H, 5-year OS 60.5% vs 58.0% (p < 0.001). In stage II MSI-H CC R was more common than left, 78.3 % (n = 3223) vs 21.7% (n = 892). There was no significant difference in survival between stage II MSI-H L vs R (5-year OS 76.2% vs 74.7%, p = 0.1578). Stage II MSS CC R was more common than L, 56.0% (n = 7571) vs 44.0% (n = 5943), and survival was better in L vs R (5-year OS 73.2% vs 70.8%, p = 0.0029). Stage III MSI-H CC was more common in R than L, 75.6% (n = 2397) vs 24.4% (n = 774) and survival was better in L (5-year OS 62.5% vs 56.5%, p = 0.0026). Stage III MSS CC was more common in R than L, 51.6% (n = 7366) vs 48.4% (n = 6905), and survival was better in L vs R (5-year OS 67.0% vs 54.4%, p < 0.001). Conclusions: Survival was better in left sided tumors compared to right in stage II MSS, stage III MSS and stage III MSI-H CC.