OBJECTIVE: This study aimed to compare the short-term prophylactic efficacy of greater occipital nerve (GON) blockade in menstrual migraine (MM) subgroups and evaluate the long-term effects on patients' quality of life. METHODS: In this prospective study, 33 patients diagnosed with MM (15 with pure menstrual migraine [PMM] and 18 with menstrually related migraine [MRM]) received bilateral GON blockade once a month, one week before menstrual bleeding, for three months. Patients were evaluated before treatment (month 0) and after treatment completion (months 3 and 6) using the Visual Analog Scale (VAS), Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), and Beck Depression Inventory (BDI) scores. RESULTS: MRM patients had a lower age of MM onset (p = 0.024), higher headache frequency (p = 0.004), and increased medication overuse (p = 0.027) compared to PMM patients. After GON blockade, significant improvements were observed in VAS, HIT-6, MIDAS, and BDI scores in both subgroups, with no significant differences between them. The improvement persisted during the medication-free follow-up period (months 3-6). Patients with mild or no depression showed a more substantial increase in quality of life. Patients experiencing a 50% reduction in headache days demonstrated significant improvement in BDI scores. CONCLUSION: GON blockade may be an effective option for short-term and long-term prophylaxis in the treatment of MM, reducing the frequency and severity of headaches and improving quality of life and psychological state. Further research with larger patient cohorts and placebo-controlled trials is necessary to validate these findings.