Background: Pharmaceutical treatments are necessary for the treatment of histamine-mediated responses such as urticaria and allergic rhinitis. The present study was cost analysis of second- generation antihistamines. Materials & Methods: 8 antihistamines produced by several pharmaceutical companies was priced from highest to lowest. For every medication, the cost ratio and % change in cost were computed. Results: WHO (DDD)(mg), no. of manufacturing brands, least expensive INR and most expensive INR for levocetirizine HCL found to be 5 mg, 188, 8.90 and 90.0 respectively. For desloratadine, it was 5 mg, 34, Rs. 26 and Rs. 94, for Ebastine, it was 10 mg, 13, Rs. 44 and Rs. 96, for Mizolastine, it was 10 mg, 3, Rs. 40 and Rs. 152, for Bepotastine, it was 10 mg, 7, Rs. 100 and Rs. 110.2, for Cetirizine dihydrochloride, it was 10 mg, 132, it was Rs. 2 and Rs. 85.0, for Loratadine, it was 10 mg, 59, Rs. 18 and Rs. 102.4 and for Fexofenadine, it was 120 mg, 88, Rs. 27.2 and Rs. 170.6 respectively. The cost ratio and cost variation (%) of levocetirizine HCL was 10 and 901, for Desloratadine was 3.54 and 256, for Ebastine was 2.0 and 118.4, for Mizolastine was 3.82 and 284.6, for Bepotastine was 1.2 and 10.4, for Cetirizine dihydrochloride was 42.4 and 4012.6, for Loratadine was 5.2 and 448.2 and for Fexofenadine was 6.2 and 504.2. The difference was significant (P< 0.05). Conclusion: The pricing of antihistamine medications varies greatly, according to this study, particularly when it comes to second-generation medications that are sold in India. Healthcare practitioners must use affordable medications to lessen the financial strain on society.