BACKGROUND: The impact of adjuvant chemotherapy (AC) on outcomes in real-world patients with locally advanced rectal cancer (LARC) remains uncertain. METHODS: Consecutive patients with LARC (stage II/III) undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were identified in the Canadian Health Outcomes Research Database. The impact of AC on clinical outcomes, including disease-free survival (DFS) and overall survival (OS), was evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: A total of 1448 patients had sufficient data available to be included for analysis with 1085 (74.9%) receiving AC. Of AC patients, 40.5% received oxaliplatin-based treatments. With a median follow-up of 66.43 months, the 5-year DFS rate was 67.7% (95% CI: 64.5-70.1%) vs. 58.7% (95% CI: 52.8-64.2%) in the AC group and non-AC group, respectively ( < 0.001). The 5-year OS rate of the whole cohort was 74.3% (95% CI: 71.5-76.85%) while the 5-year OS rate of the AC group was 77.8% (95% CI: 74.7-80.6%) compared with 63.8% (95% CI: 57.9-69.2%) for the non-AC group ( < 0.001). On multivariate analysis, patients who received AC had improved DFS (HR 0.6, 95% CI: 0.49-0.73, < 0.001) and OS (HR 0.46, 95% CI: 0.36-0.58, < 0.001). CONCLUSIONS: This large multi-institutional database analysis supports the use of AC in real-world LARC patients treated with nCRT followed by surgical resection.