Aim: To assess the effectiveness of Methotrexate v/s Dapsone/ASST in treating Chronic Urticaria. Materials and methods: A prospective comparison research was conducted on 200 patients with chronic urticaria chosen from those visiting the outpatient clinic at the Department of Dermatology. The patients were randomly assigned to one of four therapy groups based on their Urticarial Activity Score (UAS) and Dermatology Life Quality Index (DLQI). Group A was comprising patients who was given oral Dapsone 50 mg for a period of 12 weeks. Group B was comprising patients who was given oral Methotrexate 10 mg (in 4 divided doses at 12 hourly interval) per week for a period of 12 weeks. Group C was comprising patients who was given Treated with ASST (Autologous Serum Skin Therapy) – 2ml of autologous serum deep intramuscular injection once a week for 9 weeks. In addition to these, patients in all the groups were prescribed Antihistamines. Group D was be the control group who was receive only Antihistamines. Results: More than 80% of patients treated with ASST had good response to treatment while only 50% of those treated with dapsone and 30% of those treated with methotrexate had good response to treatment. Poor response was seen in 4% of ASST and Dapsone patients compared to the 18% in patients receiving Methotrexate. This is still better than the 64% with poor response in the control group. The mean DLQI score across all the treatment groups when compared showed that, patients treated with ASST had the fastest and the maximal response. Both the initial response and the end point was better in ASST patients. Control group patients showed no significant improvement in DLQI score. The dapsone and methotrexate treated patients had similar response profile but there was a difference in the number of patients responding. Conclusion: We determined that ASST may be regarded as the first therapy option for individuals with chronic urticaria, particularly for those who test positive for Autologous Serum Skin Test. Dapsone may be an option for people who do not respond to standard therapy. Methotrexate is advised for individuals who have not responded to previous treatment options and is considered a last option.