Objective: Children in developing countries are at a high risk for zinc deficiency. Supplemental zinc has previously been shown to provide therapeutic benefits in diarrhea. The objective of this study was to examine the efficacy and safety of supplemental oral zinc therapy during recovery from acute or persistent diarrhea. Methods: We conducted a meta-analysis of randomized, controlled trials to compare the efficacy and safety of supplementary oral zinc with placebo in children with acute and persistent diarrhea. Results were reported using a pooled relative risk or a weighted mean difference. A total of 22 studies were identified for inclusion: 16 examined acute diarrhea (n = 15,231), and 6 examined persistent diarrhea (n = 2968). Results: Mean duration of acute diarrhea and persistent diarrhea was significantly lower for zinc compared with placebo. Presence of diarrhea between zinc and placebo at day 1 was not significantly different in acute diarrhea or persistent diarrhea trials. At day 3, presence was significantly lower for zinc in persistent diarrhea trials (n = 221) but not in acute diarrhea trials. Vomiting after therapy was significantly higher for zinc in 11 acute diarrhea trials (n = 4438) and 4 persistent diarrhea trials (n = 2969). Those who received zinc gluconate in comparison with zinc sulfate/acetate vomited more frequently. Overall, children who received zinc reported an 18.8% and 12.5% reduction in average stool frequency, 15.0% and 15.5% shortening of diarrhea duration, and a 17.9% and 18.0% probability of reducing diarrhea over placebo in acute and persistent trials, respectively. Conclusions: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea; however, the mechanisms by which zinc exerts its antidiarrheal effect have not been fully elucidated.