The use of single-dose intramuscular methotrexate for the primary treatment of ectopic pregnancy is increasing in frequency in many countries. We performed a systematic review of all available studies and case reports of intramuscular methotrexate to examine the therapeutic efficacy, side-effects and complication rates of this new treatment approach. The pooled data show a successful resolution rate of 71% (95% confidence interval 58% to 81%) after a single dose of intramuscular methotrexate and 84% (95% confidence interval 77% to 90%) after 1 or 2 doses. Side-effects were experienced by 24% (95% confidence interval 9% to 47%) of patients and 10% (95% confidence interval 7% to 14%) had a ruptured ectopic pregnancy. The pooled data show that single-dose intramuscular methotrexate is associated with a high failure rate. Follow-up is prolonged and there is a significant incidence of minor side-effects. Serious complications and side-effects have occurred. The use of intramuscular methotrexate should be confined to clinical trials until more evidence is obtained to support its more widespread use.