BACKGROUND Medical treatment of the rare interstitial ectopic pregnancy with methotrexate has been considered an alternative to surgical resection. AIM To determine the treatment success rate with a single-dose intravenous methotrexate/folinic acid regimen and to identify predictors of treatment outcome. METHODS A 5-year audit (April 2000-August 2005) was carried out, collecting clinical imaging data and serum beta-human chorionic gonadotrophin (beta-hCG). Time taken for complete beta-hCG resolution was recorded, and a negative beta-hCG result was used as an endpoint of successful outcome. RESULTS Of the 13 cases, two required urgent surgery for rupture on presentation. In the remaining 11 cases, intravenous methotrexate (300 mg) was used, with oral folinic acid rescue (15 mg x 4 doses). There were no side-effects. Complete beta-hCG resolution was achieved in 10 of the 11 medically treated cases (91% success rate), requiring 21-129 days. Successful outcome was seen with initial beta-hCG level as high as 106 634 IU/L and gestation sac as large as 6 cm and a live fetus. CONCLUSION The methotrexate/folinic acid regimen used as a one-dose treatment is safe and effective for unruptured interstitial pregnancy, with no side-effects and the advantage of avoiding invasive surgery. Subsequent tubal patency and reproductive function are yet to be ascertained.