BACKGROUND Neoadjuvant chemoradiotherapy (Neo-CRT) is the current standard strategy for treating locally advanced rectal cancer. However, it delays the administration of optimal chemotherapy and increases toxicity. AIM To compare the feasibility and efficacy of neoadjuvant chemotherapy (Neo-CT) and Neo-CRT for patients with locally advanced rectal cancer. METHODS The Cochrane, EMBASE, and PubMed databases were searched for relevant articles using MESH terms and free words. The hazard ratio of overall survival and the risk ratio (RR) for the pathological complete response, the sphincter preservation rate, and treatment-related adverse events were analyzed. RESULTS A total of 19 studies of 60870 patients were included in the meta-analysis. There was no significant difference in overall survival [hazard ratio = 1.09, 95% confidence interval (CI) = 0.93–1.24; P = 0.19] or the pathological complete response (RR = 0.79, 95%CI = 0.61–1.03; P = 0.086) between the Neo-CT and Neo-CRT groups. As compared to the Neo-CRT group, the incidences of anastomotic fistula (RR = 0.49, 95%CI = 0.35–0.68; P = 0.000) and temporary colostomy (RR = 0.69, 95%CI = 0.58–0.83; P = 0.000) were significantly lower in the Neo-CT group, with a simultaneous increase in the sphincter preservation rate (RR = 1.07, 95%CI = 1.01–1.13; P = 0.029). However, there was no significant difference in the tumor downstaging rate, overall complications, and urinary complications. CONCLUSION Neo-CT administration can lower the incidences of anastomotic fistula and temporary colostomy and increase the sphincter preservation rate as to compared to Neo-CRT and could provide an alternative to chemoradiotherapy for locally advanced rectal cancer.