BACKGROUND AND PURPOSE: Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment regimen for locally advanced rectal cancer (LARC) but has unavoidable radiation toxicity. With the advent of more optimized chemotherapy regimens, neoadjuvant chemotherapy (NAC) is sometimes offered as an alternative to NACRT. The purpose of this meta-analysis was to compare the short- and long-term outcomes of NAC and NACRT for LARC patients. MATERIALS AND METHODS: Eligible studies through June 15, 2023, were identified in the online databases. Short-term and long-term outcomes were synthesized. A total of 10 studies involving 14,807 patients (1714 vs. 13093) were included in this meta-analysis. RESULTS: There were no significant differences between the two groups in terms of lymphovascular invasion, perineural invasion, R0 resection, local recurrence, overall survival, disease-free survival, or grade 3-4 adverse events. The NAC group had a lower rate of pathological complete response [OR (95% CI) = 0.61 (0.45, 0.82)] and tumor regression grade [OR (95% CI) = 0.42 (0.25, 0.70)] and a greater rate of sphincter preservation [OR (95% CI) = 1.57 (1.14, 2.16)] than did the NACRT group. In the prospective studies, no differences in pathological complete response [OR (95% CI) = 0.62 (0.35, 1.11)], tumor regression grade [OR (95% CI) = 0.72 (0.52, 1.00)], and rate of sphincter preservation [OR (95% CI) = 1.40 (0.94, 2.09)] have been found between the two groups. CONCLUSION: NAC was able to achieve similar short- and long-term outcomes as NACRT. It is worth noting that some prospective studies excluded patients with high-risk features. For those LARC patients with high-risk features, the efficacy of NAC versus NACRT needs to be further explored.