Background: B-group vitamins can potentially contribute to migraine prophylaxis through various mechanisms. We conducted a quasi-experimental study to assess the efficacy and tolerability of a combination of vitamins B1, B6, and B12 (Neurobion) for prophylaxis of menstruation-related migraine attacks. Methods: Women diagnosed with menstrual-related migraine, both chronic and episodic headaches, were enrolled. The patients began Neurobion therapy one week before the menstruation cycle, and repeated the injection for three consecutive months; each ampoule contained 100 mg of vitamins B1 and B6 as well as 1000 μg of vitamin B12. Neurobion was used as an add-on therapy for patients receiving the same prophylactic therapy during the last two months before the start of the study. The outcome parameter examined the severity of menstrual-related migraine attacks on a 10-point visual analog scale (VAS). Results: Three hundred eighty-three patients (169 with chronic migraine and 214 with episodic migraine) were included in the final analysis. The patients received treatment with a combination of vitamins B1, B6, and B12 with positive results. The mean intensity of menstrual-related migraine attacks was reduced from 6.7 on the 10-point VAS to 3.2 (P < 0.001) in patients with chronic migraine. The mean severity of menstrual-related migraine attacks was also reduced from 7.2 to 3.7 in patients with episodic migraine (P < 0.001). There was no significant difference in the reduction of headache severity between the two groups of migraineurs (P = 0.985). Conclusions: Neurotropic vitamins, including pyridoxine, thiamine, and cyanocobalamin yielded significant reductions in the severity of menstrual-related migraine attacks. Neurobion as a combination of vitamins B1, B6, and B12 appears to be well-tolerated and beneficial as an adjuvant in treatment and prophylaxis of menstrual-related migraine attacks. Further large-scale trials with long-term follow-up will be required to confirm our results.