The purpose of this study is to assess whether serum beta-human chorionic gonadotropin (beta-hCG) levels on day 4 following methotrexate (MTX) treatment in patients with ectopic pregnancy predict successful single-dose therapy or the need for subsequent surgical intervention. Retrospective analysis of patients with ectopic pregnancies treated with MTX (50 mg/m (2)) was conducted. Inclusion criteria for MTX management were serum beta-hCG < 15,000 mU/mL, absent fetal cardiac activity, ultrasonographic gestational sac < 3.5 cm, normal liver function tests, hemodynamically stable patient with no evidence of hemoperitoneum, and informed consent. Day 1, 4, and 7 serum beta-hCG levels were obtained. Outcome parameters included successful single-dose MTX management, the requirement for multiple treatments, and whether subsequent surgery was required. Receiver operator characteristic (ROC) curves were used. P < 0.05 was considered significant throughout. Eighty-three patients were studied. Of these, 60 patients were treated successfully with single doses, 16 patients required two doses, and two patients required three doses of MTX, and five underwent surgical management. Mean day 1 serum beta-hCG levels of patients successfully treated with single-dose MTX was 3938.5 (+/- 589.2 [standard deviation]) versus 1767.65 (+/- 1237.8) mU/mL in patients requiring multiple doses of MTX therapy, ( P < 0.0001). ROC curves for serum beta-hCG levels on days 1, 4, and 7 were 0.449, 0.592, and 0.754, respectively, indicating that only day 7 serum beta-hCG levels were associated with successful single-dose MTX therapy. Serum beta-hCG levels on day 4 of MTX in patients with ectopic pregnancy do not predict successful single-dose therapy or the need for surgery.