OBJECTIVES: To evaluate the comparative effectiveness of investigational compound ferumoxytol for the treatment of iron deficiency anaemia (IDA) associated with chronic kidney disease (CKD) compared to alternative iron replacement therapies (IRT). Primary interest was the improvement in haemoglobin (Hb) from baseline levels.  METHODS: A comprehensive systematic review was conducted to identify any randomised controlled trials investigating the efficacy of IRTs for the treatment of IDA in CKD where efficacy is defined as Hb change from baseline and IRTs included intravenous (IV) and oral treatments. Twelve electronic databases were searched up to November 2010 (language unrestricted). Two reviewers independently assessed each identified reference and conducted subsequent data extraction. Method quality of each included trial was also independently assessed in accordance with NICE guidelines. A standard meta-analysis comparing oral iron to ferumoxytol was initially conducted, reflecting the trial programme. The full network of evidence that included IV and oral iron therapies was synthesised using a mixed treatment comparison (MTC). The random effects model showed ‘predicting superiority’ to the fixed effects model and was thus utilised. Mean efficacy was estimated through analysing standardised effect sizes of trials and back-transforming data to Hb values via weighted average standard deviation.    RESULTS: Seventeen published trials and one unpublished clinical study provided the heterogeneous trial base for MTC analysis. Ferumoxytol was significantly favoured when compared to oral iron therapy by conventional meta-analysis (0.61; 95% CI=0.44,0.79; P value=<0.0001) which was supported by results from the MTC efficacy analysis (0.48; 95% CI=-1.24,2.2). Significant differences in efficacy were not observed between ferumoxytol and any of the alternative IV iron therapies. CONCLUSIONS: The results from the conventional meta-analysis showed that the model favoured investigational compound ferumoxytol, in terms of increasing Hb, in comparison to oral iron therapy and suggested a modelled equivalence to currently approved alternative IV iron treatments.