To identify risk factors for tubal rupture among ectopic pregnancies treated with methotrexate (MTX). Retrospective casecontrol analysis. An urban medical center. Eightyone women diagnosed with an ectopic gestation treated with MTX: 19 patients experienced subsequent tubal rupture, and 62 patients experienced ectopic resolution. None. Predictive variables including serial human chorionic gonadotropin (hCG) values. The hCG incremental rate before as well as after MTX administration was positively associated with tubal rupture. HCG values prior to ectopic diagnosis that increased at least 66%over 48 hours and rising hCG values after treatment with methotrexate were independent predictors of tubal rupture. A disproportionate number (47%) of ectopic pregnancies that ruptured were located in the tubal isthmus. The hCG incremental rate both before and after MTX represents an independent risk factor for subsequent tubal rupture. Concentrations of hCG before ectopic diagnosis that increased at least 66%over 48 hours, or persistently rising hCG concentrations after treatment with MTX, may lower the threshold for surgical intervention. Implantation site may represent an unidentifiable risk factor for tubal rupture. To identify risk factors for tubal rupture among ectopic pregnancies treated with methotrexate (MTX). Retrospective casecontrol analysis. An urban medical center. Eightyone women diagnosed with an ectopic gestation treated with MTX: 19 patients experienced tubal rupture, and 62 patients experienced Predictive variables including serial human chorionic gonadotropin (hCG) values. The hCG incremental rate before as well as after MTX administration was positively associated with tubal rupture. HCG values ​​prior to ectopic diagnosis that increased at least 66% over 48 hours and rising hCG values ​​after treatment with methotrexate were independent predictors of tubal rupture. A disproportionate number (47%) of ectopic pregnancies that ruptured were located in the tubal isthmus. The hCG incremental rate both before and after MTX represents an independent risk factor for subsequent tubal rupture. Concentrations of hCG before ectopic diagnosis that increased at least 66% over 48 hours, or persistently rising hCG concentrations after treatment with MTX, may lower the threshold for surgical intervention. Implantation site may represent an unidentifiable risk factor for tubal rupture.