Numerous preclinical studies have suggested that micronutrient status is associated with the progression of human immunodeficiency virus (HIV) disease, but results from observational studies are still controversial. The objective was to systematically review the efficacy of multiple micronutrient supplementation on mortality and morbidity in HIV-infected adults. A comprehensive search of the PubMed/MEDLINE, EMBASE and Cochrane Library was performed. Six randomized controlled trials assessing the effect of multiple micronutrient supplementation on HIV-infected adults were included. Relative risk was used as an effect measure to compare the intervention and control groups with fixed-effects or random effects models. Sensitivity analyses were applied to further evaluate heterogeneity. Multiple micronutrient supplementation decreased the mortality and morbidity of HIV-infected adults nonstatistically significantly (RR=0.90; 95% CI, 0.80 to 1.02; p=0.09). Sensitivity analyses revealed that multiple micronutrient supplementation decreased the mortality and morbidity of adults infected with HIV alone statistically significantly (RR=0.75; 95% CI, 0.58 to 0.95; p=0.02), but not adults infected with both HIV and pulmonary tuberculosis (RR=0.97; 95% CI, 0.84 to 1.11; p=0.65). Multiple micronutrient consumption was correlated with reduction of the mortality and morbidity of HIV-infected adults, at least those in developing countries and infected with HIV alone, and should be prescribed by local doctors for those in earlier stages especially.Numerous preclinical studies have suggested that micronutrient status is associated with the progression of human immunodeficiency virus (HIV) disease, but results from observational studies are still controversial. The objective was to systematically review the efficacy of multiple micronutrient supplementation on mortality and morbidity in HIV-infected adults. A comprehensive search of the PubMed/MEDLINE, EMBASE and Cochrane Library was performed. Six randomized controlled trials assessing the effect of multiple micronutrient supplementation on HIV-infected adults were included. Relative risk was used as an effect measure to compare the intervention and control groups with fixed-effects or random effects models. Sensitivity analyses were applied to further evaluate heterogeneity. Multiple micronutrient supplementation decreased the mortality and morbidity of HIV-infected adults nonstatistically significantly (RR=0.90; 95% CI, 0.80 to 1.02; p=0.09). Sensitivity analyses revealed that multiple micronutrient supplementation decreased the mortality and morbidity of adults infected with HIV alone statistically significantly (RR=0.75; 95% CI, 0.58 to 0.95; p=0.02), but not adults infected with both HIV and pulmonary tuberculosis (RR=0.97; 95% CI, 0.84 to 1.11; p=0.65). Multiple micronutrient consumption was correlated with reduction of the mortality and morbidity of HIV-infected adults, at least those in developing countries and infected with HIV alone, and should be prescribed by local doctors for those in earlier stages especially.