We aimed to synthesise evidence to assess the effect and safety of NaFeEDTA on Hb and serum ferritin in Fe-deficient populations. We performed a systematic review, identifying potential studies by searching the electronic databases of Medline, Cochrane Library, Embase, WHO Library and China National Knowledge Infrastructure. We also hand-searched relevant conference proceedings and reference lists. Finally, we contacted experts in the field. The selection criteria included randomised or quasi-randomised controlled trials of NaFeEDTA compared with placebo. Hb, serum ferritin and adverse effects were outcomes of interest. Inclusion decisions, quality assessment and data extraction were performed by two reviewers independently. Seven studies met the inclusion criteria. All included studies assessed the effect of NaFeEDTA on Hb concentration, four studies assessed the effect on serum ferritin concentration, and one study on serum Zn concentration. After the intervention, Hb concentration and serum ferritin concentration were both higher in the NaFeEDTA group compared with the control group. For Hb, data from six studies could be pooled and the pooled estimate (weighted mean difference) was 8.56 (95 % CI 2.21, 14.90) g/l (P = 0.008). For serum ferritin, data from four studies could be pooled and the pooled difference was 1.58 (95 % CI 1.20, 2.09) microg/l (P < 0.001). Subgroup analysis indicated that a lower baseline Hb level was associated with a greater increase in Hb concentration. No significant difference in serum Zn concentration was found. We concluded that NaFeEDTA increased both Hb concentration and serum ferritin concentration substantially in Fe-deficient populations, and could be an effective Fe preparation to combat Fe deficiency.