Objective To investigate the effects of two formulations of artesunate, and to provide evidence for the WHO Model List of Essential Medicines. Methods We searched The Cochrane Library (2006, Issue 4), MEDLINE ( 1966 to 2007), EMbase (1988 to 2007), CBM (1978 to 2007), VIP (1989 to 2007) and CNKI (1994 to 2007). Randomised trials comparing the two formulations of artesunate with other drugs were eligible for inclusion. We applied the methods of The Cochrane Collaboration to assess the effects of artesunate, compared to placebo and active controls. Results Eleven trials were included, of which 6 compared intravenous artesunate with intravenous quinine. The quality of each study was high, 6 out of the 11 studies were graded A according to the criteria of The Cochrane Collaboration. The other 5 were graded B. The meta-analysis suggested that the mortality rate was lower in the intravenous artesunate group than in the intravenous quinine group [RR 0.65, 95%CI (0.52, 0.80), Plt;0.0001]. Three trials compared intravenous artesunate with artemisinin suppositories. These trials generated similar estimates and confidence intervals for mortality rates, showing no significant difference between the two treatments [0.94 (0.35 to 2.56), 0.58 (0.19 to 1.74) and 2.00 (0.39 to 10.26)]. Two trials compared intravenous artesunate and intramuscular artesunate, and no significant difference in mortality rate was identified between the two treatment groups [RR 1.50, 95%CI 0.52 to 4.31]. Mortality rates were not statistically significantly different for intravenous artesunate compared to alternative drugs. No significant adverse drug reactions were observed. Conclusions Artesunate is effective and safe in the treatment of severe malaria.