Introduction: Ectopic pregnancy is defined as the implantation of a fertilized ovum outside the endometrial cavity. The most common site is the fallopian tube. The incidence of ectopic pregnancy is 1–2% of all pregnancies. Methotrexate is the most commonly used drug for the medical management of ectopic pregnancy. It is a folic acid antagonist that prevents the growth of rapidly dividing cells including trophoblasts and fetal cells by interfering with DNA synthesis. Aim and objective: To study initial and day 4 β-hCG levels as predictors of outcome of single-dose methotrexate therapy in the medical management of ectopic pregnancy. Materials and methods: Thirty patients after confirmed diagnoses of tubal ectopic pregnancy were enrolled in the study. β-hCG was estimated using a sequential two-step immunoenzymatic (sandwich) assay. Results: Out of 30 women who received inj MTX on day 0, 19 (63.3%) women were treated successfully with a single dose of methotrexate (group I), 8 (26.6%) women required a second dose of methotrexate, and 3 (10%) women required surgery. Women who required a second dose or surgery were treatment failure (group II) (36.6%) with a single-dose methotrexate regimen. The mean initial β-hCG β-hCG level was 2294.92 ± 1162.93 mIU/mL in group I and 3831.18 ± 1066.83 mIU/mL in group II. The difference of mean was statistically significant between group I and group II on day 0, day 4, and day 7. Conclusion: Results in the present study favor therapeutic intervention with a second dose of methotrexate on day 4 against day 7 as in the current protocol in women with a rising trend of β-hCG between day 0 and day 4. However, due to the small sample size, further studies are needed to validate these findings.