Background Ectopic pregnancy was recorded as the fourth principal cause of maternal death in Malaysia in 2019. Early diagnosis and use of methotrexate treatment proved to be safe and effective alternatives to surgical treatment. This study investigates the success rate of methotrexate treatment for ectopic pregnancy in a tertiary hospital in Malaysia. Methods This was a retrospective review of 73 patients with ectopic pregnancies treated with methotrexate according to a single-dose protocol from January 2009 until November 2019. The diagnosis of ectopic pregnancy was made using a combination of transvaginal scan and serial serum β-hCG levels. Their clinical and demographic data were reviewed. Serum β-hCG levels were measured at pre- and post-treatment to determine the rate of successful resolution. Results The overall success rate was 87.7% (64/73 patients) with methotrexate treatment. Fifty-six patients (76.7%) were successfully treated with a single dose of methotrexate, and eight patients (11.0%) required a second dose of methotrexate. There was no relation between socio-demographic, pre-treatment β-hCG levels, ectopic mass size, and treatment efficacy. Smaller size of ectopic pregnancy (adjusted OR=29.23; 95% CI: 2.69, 317.90; P=0.006) and absence of free fluid at the pouch of Douglas (POD) (adjusted OR=27.31; 95% CI: 2.84, 262.32; P=0.004) was found to increase the likelihood of overall treatment success. Absence of fetal cardiac activities was found to increase the likelihood of first-dose methotrexate treatment success (OR=10.20; 95% CI: 1.93, 53.79; P=0.006). Conclusions Early diagnosis of ectopic pregnancy may reduce morbidity and mortality. In carefully selected cases, methotrexate treatment has been proven to be cost-effective and avoided risks associated with surgery and anaesthesia.