Objective: To evaluate the conservative management of pain after systemic methotrexate therapy for ectopic pregnancy; identify prognostic factors for success; and compare hCG resolution time for patients with and without pain. Methods: A retrospective review of patients with ectopic pregnancy requiring evaluation for pain after receiving single-dose methotrexate therapy is performed. Results of hematocrits, ultrasound findings, hCG levels, time for hCG levels to reach less than 15 mIU/mL, and outcome were noted. Results: Fifty-three patients with 64 episodes of pain were identified. Seven hospitalized patients required surgery during admission. Two previously hospitalized and one outpatient also ultimately underwent surgery. For hospitalized patients, there were no statistical differences between patients who did or did not undergo surgery during admission for any variable studied, including the presence of free peritoneal blood or rebound tenderness. However, comparison of hospitalized and nonhospitalized patients showed those with rebound tenderness were more likely to be admitted. Hospitalized patients not requiring surgery had shorter resolution time than nonhospitalized patients. For hospitalized and nonhospitalized patients, the median time from treatment to presentation for pain was 8 days. Conclusion: The occurrence of pain following methotrexate therapy for ectopic pregnancy should not be the sole indication for surgical intervention. The majority of stable patients with pain after methotrexate therapy, even with rebound or free peritoneal fluid, can be treated successfully without surgery, either in hospital with close observation for severe pain or as outpatients for patients with less severe pain.