Objective: To analyze the effect of promethazine hydrochloride combined with betahistine mesylate in the treatment of vertigo. Methods: 96 patients with vertigo who received treatment in our hospital from January 2023 to January 2024 were selected as the study objects. Patients were divided into promethazine group, betahistine group and combination group by random number table, with 32 cases in each group. Promethazine group was treated with promethazine hydrochloride. Betahistine group was treated with betahistine mesylate. The combined group was treated with promethazine hydrochloride and betahistine mesylate. The efficacy, improvement time of clinical symptoms, cerebral blood flow velocity and recurrence of the three groups were analyzed and compared. Results: The total effective rate of combined group was significantly higher than that of promethazine group and betahistine group (P < 0.05). There was no significant difference in the total effective rate between propromazine group and betahistine group (P > 0.05). The improvement time of clinical symptoms of deafness, tinnitus, sweating and dizziness in combination group was significantly shorter than that in propromazine group and betahistine group (P < 0.05), while the improvement time of clinical symptoms of deafness, tinnitus, sweating and dizziness in betahistine group was significantly shorter than that in propromazine group (P < 0.05). After 7 days of treatment, the basilar artery blood flow velocity and left vertebral artery blood flow velocity of the three groups were significantly increased compared with before treatment, and the basilar artery blood flow velocity and left vertebral artery blood flow velocity of the combined group were significantly higher than those of propromazine group and betahistine group, and the basilar artery blood flow velocity and left vertebral artery blood flow velocity of the combined group were significantly higher than those of propromazine group (P < 0.05). The recurrence rate of combination group was significantly lower than that of promethazine group and betahistine group (P < 0.05), but there was no significant difference between promethazine group and betahistine group (P > 0.05). Conclusion: Promethazine hydrochloride combined with betahistine mesylate in the treatment of vertigo can improve the curative effect, promote the relief of clinical symptoms, accelerate cerebral blood flow and reduce recurrence.