Our objective is to describe off-label use of methotrexate in ectopic ă pregnancy treatment using evidence based medicine. The patient group ă includes all women with a pregnancy outside the usual endometrium, or of ă unknown location. ă Method used was a Medline search on ectopic pregnancy managed using ă methotrexate treatment; evidence synthesis was done based on this ă current literature analysis. ă Level of evidence (LE) were given according to the centre for evidence ă base medicine rules. Grade was proposed for guidelines but no ă recommendation was possible as misoprostol is off label use for all the ă indications studied. ă In the absence of any contraindication, the protocol recommended for ă medical treatment of ectopic pregnancy is a single intramuscular ă injection of methotrexate (MTX) at a dosage of 1 mg/kg or 50 mg/m(2) ă (Grade A). It can be repeated once at the same dose should the hCG ă concentration not fall sufficiently. Pretreatment laboratory results ă must include a complete blood count and kidney and liver function tests ă (in accordance with its marketing authorization). ă MTX is an alternative to conservative treatment such as laparoscopic ă salpingotomy for uncomplicated tubal pregnancy (Grade A) with ă pretreatment hCG levels <= 5000 IU/1(Grade B). Expectant management is ă preferred for hCG levels < 1000 IU/I or in the process of spontaneous ă decreasing (Grade B). ă Intramuscular MTX is also recommended after the failure of surgical ă salpingotomy (Grade C) or immediately after surgery, if monitoring is ă not possible. Except in special circumstances, a local insitu ă ultrasound-guided MTX injection is not recommended for unruptured tubal ă pregnancies (Grade B). ă In situ MTX is an option for treating cervical, interstitial, or ă cesarean-scar pregnancies (Grade C).. In pregnancies of unknown location ă persisting more than 10 days in an asymptomatic woman who has an hCG ă level > 20001U/1, routine MTX treatment is an option. ă MTX is not indicated for combination with treatments such as ă mifepristone or potassium. (C) 2016 Published by Elsevier Ireland Ltd.