We conducted a systematic review and meta-analysis to estimate the efficacy of darbepoetin alpha (DA) for treatment of myelodysplastic syndrome (MDS)-related anaemia. Eligible studies were prospective, interventional, and reported World Health Organization, French-American-British, or International Prognostic Scoring System (IPSS) criteria. Outcomes included erythroid response rate (primary); haemoglobin response; change in haemoglobin, transfusion status, and quality-of-life (QoL); and safety. Ten studies (N = 647) were analysed. Erythroid response rate range was 38–72%; median response duration range was 12–51+ months. Patients with erythropoietin (EPO) <100 iu/l had 35% [95% confidence interval (CI): 22–48%; P < 0·001) better response than patients with EPO >100 iu/l. Erythropoesis-stimulating agent (ESA)-naïve patients had 17% (95% CI: 3–32%; P = 0·022) greater response rate than those previously treated with ESA. Nonetheless, previously treated patients had response rates of 25–75%. Higher baseline haemoglobin levels, higher dose, transfusion-independence and low-risk IPSS status were reported by several studies to be associated with better response. QoL, transfusion rates and haemoglobin levels improved with treatment. Hypertension, thromboembolism and progression to acute myeloid leukaemia were reported in 2%, 1% and 1% of patients, respectively. This meta-analysis suggests that DA treatment can be useful for improving erythroid response in MDS patients with anaemia, even among patients previously treated with ESA.