Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd Edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.