Abstract Background Infections are major causes of morbidity and mortality worldwide. Micronutrients have important functions in the body's immune system. This systematic review examined the evidence from randomized controlled trials (RCTs) on whether multivitamin and multimineral supplementation is effective in reducing infection. Methods Electronic databases searched: Cochrane Controlled Trials Register, EMBASE, MEDLINE, BIOSIS, CAB abstracts. Hand searching of nutrition journals and reference lists was carried out. RCTs and quasi-randomized trials of supplementation of adults with at least two vitamins or minerals or a combination were selected. Study results were combined in meta-analysis plots where appropriate. Results Twenty studies were included in the review. Small numbers were available for each meta-analysis. Results are presented here without the Chandra group studies. No significant difference was found in the number of episodes of infection in older people (≥65 years) between those supplemented and those not supplemented; (WMD) 0.06 [95% confidence interval (CI) −0.04, 0.16], P = 0.25. In other adults groups, there were significantly less episodes of infection in those supplemented; (WMD) −1.20 (95% CI −2.08, −0.32), P = 0.008. There was no significant difference between those older people supplemented and those not supplemented in the number with at least one infection; relative risk (RR) 0.98 (95% CI 0.86, 1.11), P = 0.77. Similarly, there was no significant difference in the numbers in other adult groups who had at least one episode of infection between those supplemented and those taking placebo; (RR) 0.81 (95% CI 0.65, 1.00), P = 0.06. Subgroup analyses suggested that supplemented people aged 65 years or over may benefit more if they are undernourished and supplemented for over 6 months, WMD −0.67 infections (95% CI −1.24, −0.10), P = 0.02. Conclusion Further large trials are needed, particularly in undernourished older people. Trials of supplementation periods of over 6 months are recommended.