Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20–50 years, Sinclair (II–IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients’ self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P< 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P< 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P< 0.05). Side effects were not significantly different between groups (P> 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients’ perspective with a good safety profile (NCT04481412, study start date: July 2020).