Objective: To estimate the failure rate of medical treatment and to identify variables associated with treatment failure in patients with tubal pregnancy and an initial serum level of human chorionic gonadotropin (HCG) over 10,000 IU/L. Methods: The inclusion criteria were tubal pregnancy diagnosed using ultrasonography, primary treatment of intramuscular methotrexate injection at one of the four institutions between January 2003 and December 2011, a serum HCG level within two days before treatment >10,000 IU/L, and follow-up data to determine treatment success or failure. Exclusion criteria were other primary treatments besides intramuscular methotrexate injection. The clinicopathologic data of 36 patients were collected and analyzed. Results: Medical treatment failed and surgery was performed in 19 (53%) patients. In univariable analysis, age, parity, and size of the gestational sac were associated with treatment failure, but none of the variables were associated with treatment failure in multivariable analysis. The failure rate in the subgroup with age<33 years and size of gestational sac ${geq}1.1cm$ was significantly higher than those of the other subgroups (82% vs. 41% [mean of the other subgroups], respectively). Conclusion: Patients with a serum HCG level >10,000 IU/L who received medical treatment had a high failure rate. Among them, patients aged<33 year and with a gestational sac ${geq}1.1cm$ had an extremely high failure rate.