Background: Standard adjuvant chemotherapy regimens for Stage III colorectal cancer (CRC) include FOLFOX/CAPOX, 5-FU/capecitabine, or observation alone. There is uncertainty around the therapeutic benefit of adding oxaliplatin to fluorouracil in older adults over the age of 70 with Stage III CRC, including in those with mismatch repair–deficient (MMR-D) CRC. In this single institutional study, we evaluate progression free survival (PFS) across a 12-year period in patients who receive FOLFOX/CAPOX or 5-FU/capecitabine compared to active surveillance in older adults with MMR-D Stage III CRC. Methods: We identified patients diagnosed with MMR-D Stage III CRC after the age of 70 who received care at our institution and affiliates between 2005-2019. We performed a retrospective chart review of patient outcomes during the 12-year follow up period based on chemotherapy regimen to determine PFS. Patients without MMR-D staining performed at initial time of diagnosis had MMR protein immunohistochemistry performed currently and included in the analysis. Results: Among patients with MMR-D stage III CRC, 50%, 62.5%, and 76% of patients were alive at the end of year 12 with no disease progression in the observation, 5-FU/capecitabine, and FOLFOX/CAPOX groups. The PFS probabilities at one year are 69.6%, 87.5%, and 87.0%, and at five years are 41.8%, 62.5%, and 87.0% in these groups, respectively. Finally, there was a statistically significant difference (P=0.039) in PFS across all chemotherapy regimens in the MMR-D cohort. Conclusions: Based on this study, older adult patients with stage III MMR-D colorectal cancer have an improved progression free survival when treated with oxaliplatin containing chemotherapy compared to active surveillance alone.