Objective To explore the clinical effect of intramuscular injection of methotrexate on hysteroscopic treatment of endogenous cesarean scar pregnancy (CSP). Methods A prospective analysis was conducted on 94 patients diagnosed with endogenous CSP who visited the Department of Gynecology in Liuzhou Workers’ Hospital between January 2013 and January 2018, and they were randomly divided into two groups, the intramuscular injection of methotrexate followed by hysteroscopic surgery group (the methotrexate group, n=39) and the direct hysteroscopic surgery group (the non-methotrexate group, n=55). The operation time, intraoperative blood loss, surgical complications, length of hospital stay, hospitalization expenses, the recovery time of blood human chorionic gonadotropin (HCG) and treatment outcomes of the two groups were compared. The normally distributed data were expressed as mean±standard deviation, and the non-normally distributed data were expressed as median (lower quartile, upper quartile). Results There was no statistically significant difference in age, gestational sac diameter, uterine scar thickness, number of cesarean sections, time from cesarean section to present, time of menopause, or preoperative blood HCG value between the two groups (P>0.05). There was no statistically significant difference in intraoperative blood loss [75 (35, 120) vs. 65 (35, 130) mL, P=0.821], incidence of complications (5.1% vs. 5.5%, P=1.000), postoperative blood HCG recovery time [(5.22±2.17) vs. (4.96±1.81) weeks, P=0.559] or the effective rate of treatment (94.9% vs. 90.9%, P=0.747) between the two groups. The methotrexate group had longer operation time [43 (34, 55) vs. 32 (28, 35) min, P=0.001], longer length of hospital stay [(10.89±1.42) vs. (5.82±1.47) d, P<0.001], and higher hospitalization cost [(8596.46±3336.59) vs. (7058.84±2638.49) yuan, P=0.014]. Conclusion For patients with endogenous CSP, intramuscular injection of methotrexate before hysteroscopic surgery is not necessary, for it has no significant impact on the treatment effect, instead, it may prolong the operation time and length of hospital stay, and increase the hospitalization cost.