Objective: To test the hypothesis that endometrial stripe thicker than 12 mm increases treatment failure of single-dose methotrexate for the management of ectopic pregnancy. Study design: Seventy-three patients with ectopic pregnancy and measured pretreatment endometrial stripe were divided into two groups based on the endometrial stripe thickness (>12 mm or ≤ 12 mm). All patients were candidates for single-dose methotrexate treatment. Variables analyzed between the two groups were endometrial stripe thickness, initial beta human chorionic gonadotropin level (hCG), size of the ectopic mass, presence of fetal heart tones, previous ectopic pregnancy, and clinical outcomes. Results: Sixty patients had endometrial stripe thickness ≤ 12 mm and 13 patients >12 mm. The two groups were similar in initial hCG, size of ectopic mass, presence of fetal heart tones and rate of previous ectopic pregnancy. The failure rate was significantly higher in the group with endometrial stripe >12 mm compared to the group ≤ 12 mm (n=7, 53% vs. n=3, 5%, P<0.01). The endometrial stripe was significantly thicker in the group with endometrial stripe thickness >12 mm compared to the group ≤ 12 mm (mean ± SD, 17.64±5.82 mm vs. 7.69±2.82 mm, P<0.01). Conclusion: Endometrial stripe thicker than 12 mm increases the risk for treatment failure with single-dose methotrexate. © Springer-Verlag 2005.