OBJECTIVE In a retrospective observational study, we evaluated the feasibility and safety of medical therapy with transabdominal ultrasound-guided injection of methotrexate (MTX) into the gestational sac (GS) in patients with interstitial ectopic pregnancies. METHODS Fourteen interstitial ectopic pregnancies were treated with transabdominal ultrasound-guided injection of MTX (25 mg). All patients were hemodynamically stable. In all patients, the 10-cm distance between the GS and vaginal fornices was ≥10 cm, making transvaginal injection difficult. To evaluate feasibility and safety of the procedure, we assessed complications clinically and with imaging during a 1-year follow-up. RESULTS In all 14 patients, MTX injected locally into the GS successfully terminated the interstitial pregnancy, thereby avoiding surgery. There was no complications during follow-up. CONCLUSIONS The successful outcome in our patients suggests that the transabdominal route is feasible and safe as a nonsurgical option for terminating an ectopic interstitial pregnancy in patients in whom the transvaginal route is contraindicated or difficult, provided the patients are properly selected and operators have sufficient experience with the technique.