Aim: To evaluate the efficacy of Methotrexate versus Dapsone/ASST in the treatment of chronic urticaria. Materials & methods: A prospective comparative study done on 200 patients with chronic urticaria were selected from the patients attending out-patient clinic in Department of Dermatology. The participants were assigned in a random manner to one of four treatment groups based on their Urticarial Activity Score (UAS) and Dermatology Life Quality Index (DLQI) calculations. Group A was comprise patients who were given oral Dapsone 50 mg for a period of 12 weeks. Group B was comprise patients who were given oral Methotrexate 10 mg (in 4 divided doses at 12 hourly interval) per week for a period of 12 weeks. Group C was comprise patients who were given Treated with ASST (Autologous Serum Skin Therapy) – 2ml of autologous serum deep intramuscular injection once a week for 9 weeks. Group D was the control group who were received only Antihistamines. Results: More than 72% of patients treated with ASST had good response to treatment while only 56% of those treated with dapsone and 30% of those treated with methotrexate had good response to treatment. Poor response was seen in 6% of ASST and Dapsone patients compared to the 20% in patients receiving Methotrexate. This is still better than the 52% with poor response in the control group. Conclusion: It has been determined that autologous serum skin test (ASST) may be regarded as an initial therapeutic approach for individuals diagnosed with chronic urticaria, particularly among those who exhibit positive results on the ASST. Dapsone may be regarded as a potential therapeutic option for patients who have shown resistance to conventional treatment methods. Methotrexate is typically advised as a final option for patients who have not responded to alternative treatment methods. Keywords: Methotrexate, Dapsone, ASST, Chronic Urticaria