OBJECTIVE To compare the effectiveness of single-dose methotrexate (MTX) and laparoscopic salpingostomy in the treatment of unruptured ectopic pregnancy (UEP). METHODS 75 patients entered a prospective non-randomized study. Thirty-seven women were submitted to a single-dose methotrexate (Group 1) and 38 underwent laparoscopic salpingostomy (Group 2). Methotrexate (1 mg/kg) was given intramuscularly on an out-patient basis if the beta-hCG level was < 5000 IU/I and the hematosalpinx diameter was < 3 cm and the peritoneal fluid < 300 cm3 on TVS. The follow-up consisted of serial clinical examinations, beta-hCG assays, liver tests and blood cell counts. Laparoscopic salpingostomy was decided in other cases of UEP or when patients refused or could not comply with the follow-up. RESULTS Group 1 patients (91.8%) were cured with 1-3 doses of MTX, the remainder required a laparoscopy. Seventy-three percent of them were treated on an out-patient basis. The mean time to resolution of hCG was 26.7 days. The initial beta-hCG level significantly correlated with the necessity of a surgical option and the time to resolution of beta-hCG. Whenever beta-hCG was < 3600 IU/l, all patients were cured with a single injection, without hospitalization and with a follow-up of < 27 days. Group 2 patients (81.6%) were cured with laparoscopy and 15.8% required a MTX injection for persistent EP. The mean hospital stay was significantly longer than for those that required the MTX injection (2.7 vs. 0.6; P = 0.0001), but the follow-up was shorter and required significantly less clinical examinations, sonograms and biologic tests. Finally the effectiveness of single-dose MTX and laparoscopic salpingostomy were similar (P = 0.2, 95% CI of the difference: -0.15-0.04). CONCLUSIONS Single-dose MTX was as effective as laparoscopy in the treatment of UEP. A rigorous selection of the patients for the treatment option is mandatory to guarantee high success rates, in an out-patient basis and a short follow-up.