OBJECTIVES: The objective of this systematic review was to summarize the evidence of calcium and magnesium (CaMg) infusions in the prevention of oxaliplatin-induced neuropathy on the basis of prospective randomized controlled trials (RCTs). METHODS: A systematic search included MEDLINE and CENTRAL, plus major oncology conferences, and identified RCTs evaluating CaMg. Efficacy endpoints were chronic neurotoxicity measured with National Cancer Institute Common Terminology Criteria for Adverse Events grades and the oxaliplatin-specific scale (OSS). Data were synthesized using a random effects model. RESULTS: A total of 5 trials with 694 evaluable patients were included in this analysis. The pooled result stated the outcome of the largest study included [Loprinzi et al.: J Clin Oncol 2014;32:997-1005], in which no differences were detected for the incidence of grade ≥2 neuropathy between those receiving CaMg infusions and controls [relative risk (RR) 0.81, 95% confidence interval (CI) 0.60-1.11]. Only 2 studies (n = 52) quoted an incidence of chronic neurotoxicity for all grades (with a pooled RR of 0.95 and 95% CI 0.69-1.32), with substantial statistical heterogeneity. Three studies reported an actual incidence of the OSS but, due to the detected substantial statistical heterogeneity, the studies were not pooled. CONCLUSION: The results of our systematic review demonstrated the nonbeneficial effect of CaMg infusions for the prevention of oxaliplatin-induced peripheral neuropathy.