Successful medical management of an ectopic pregnancy is inversely associated with initial hCG level. The purpose of this publication is to assess whether there is a level of hCG above which failure rate substantially increases.A systematic review and summary analysis was performed, including studies reporting methotrexate treatment outcomes as stratified by various hCG ranges.Academic medical center.Review of published information regarding patients treated with methotrexate.None.Success and failure rate of medical management.Five observational studies, including 503 women, were found that reported successes in using single-dose methotrexate stratified by initial hCG concentration. Failure rates increase with increasing hCG levels. A substantial and statistically significant increase in failure rates is seen when comparing patients who have initial hCG levels of >5,000 mIU/mL with those who have initial levels of <5,000 mIU/mL (odds ratio: 5.45; 95% confidence interval: 3.04, 9.78). The failure rate for women who had an initial concentration between 5,000 and 9,999 mIU/mL was significantly higher than that for those who had initial levels between 2,000 and 4,999 mIU/mL (odds ratio: 3.76; 95% confidence interval: 1.16, 12.33).Results support a substantial increase in failure of medical management with single-dose methotrexate when the initial hCG is above 5,000 mIU/mL. Methotrexate should be used with caution in patients with ectopic pregnancy who present with hCG levels above this level.