Objective: To evaluate the feasibility and effectiveness of fetal reduction by transabdominal intracranial KCl injection for multifetal pregnancies in the early second trimester. Methods: The data of 363 patients who underwent transabdominal fetal reduction in the Reproductive Medical Center of Peking University Third Hospital from January 2006 to December 2019 were analyzed retrospectively. According to the location of fetal reduction, they were divided into two groups: Intracranial injection group (n=196) and intrathoracic injection group (n=167). The process of fetal reduction and pregnancy outcome of the two groups were compared. Results: There was no significant difference between the two groups in the average age and the proportion of type of infertility before assisted reproductive technology, conception method, indication for fetal reduction, starting number of fetuses, reduced number of fetuses, and finishing number of fetuses (P>0.05). There was no significant difference between the two groups in the proportion of the number of puncture ≥ 2 times (12.1% vs. 8.6%, P=0.249) and the incidence of replacing puncture site (10.7% vs. 6.4%, P=0.161). The next day after fetal reduction, color Doppler ultrasound was rechecked. In the intracranial injection group and intrathoracic injection group, the incidence of fetal heartbeat recovery [3.6% (8/224) vs. 1.1% (2/187), P=0.188], the volumes of KCl used [(2.6±1.0) mL vs. (2.8±1.1) mL, P=0.079], and the abortion rate within 4 weeks after fetal reduction (1.0% vs. 0.6%, P=0.654) were of no significant difference. In addition, there was no significant difference in the total abortion rate after fetal reduction, premature delivery rate, cesarean section rate, delivery gestational week and neonatal birth weight between the two groups (P>0.05). Conclusion: Intracranial KCl injection can be an effective alternative to intrathoracic KCl injection for multifetal pregancy reduction.