A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched for relevant randomized controlled trials (RCTs) until January 31 2017. Review Manager (version 5.3) was used to analyze the data. Dichotomous data were calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8 RCTs with 6103 stage II or III rectal cancer patients were analyzed, including 2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with fluorouracil alone regimen. Compared with fluorouracil-based regimen group, oxaliplatin-based regimen group attained higher pathologic complete response (OR = 1.29, 95% CI: 1.12−1.49, P = 0.0005) and 3-year disease-free survival (OR = 1.15, 95% CI: 0.93−1.42, P = 0.21), but suffered greater toxicity (OR = 2.07, 95% CI: 1.52−2.83, P < 0.00001). Also, there were no significant differences between two regimens in sphincter-sparing surgery rates (OR = 0.94, 95% CI: 0.83−1.06, P = 0.33), 5-year disease-free survival (OR = 1.15, 95% CI: 0.93−1.42, P = 0.21) and overall survival (3-year, OR = 1.14, 95% CI: 0.98−1.34, P = 0.09; 5-year, OR = 1.06, 95% CI: 0.78−1.44, P = 0.70). In conclusion, the benefits of adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer remains controversial, and cannot be considered a standard approach.