Rheumatoid Arthritis is an autoimmune disorder of unknown etiology. There is no one stop therapy that can cure the disease. The goal of therapy in Rheumatoid arthritis is to induce prolonged remission. Disease Modifying Anti rheumatic Drugs (DMARD) are the drug of choice, can be used either in monotherapy or in combinations of DMARDs. Among all of these DMARD‘s, commonly methotrexate based combined therapy is used to control the disease. Our present study is to evaluate the response of the drug therapy on disease process and compare the efficacy of the two regimens Methotrexate + Lefunamide vs Methotrexate +Sulfasalazine +Hydroxychloroquine using ACR 20 guideline and also to study the adverse event occuring during this study period. It is a prospective observational study carried out in the department of Pharmacology and Rheumatology outpatient department of R.G. Medical College and Hospital, kolkata. Treating physicians prescribed the drugs according to the condition of the patients without any randomization. Patients were divided into two groups, Group A 60 patients who had been prescribed Methotrexate +Leflunomide, 60 patient of another group (Group B) were prescribed Methotrexate+ Sulphasalazine +Hydroxychloroquine. A questionnaire containing 20 questions (HAQ DI) were given to each patient for assessment of Physical Function at baseline and after 6 months to evaluate the response to drug therapy. After completion of therapy data were analysed by proper statistical method and it was found that our study had shown that efficacy of MTX+SSZ+HCQ (group-B) was statistically better improvement than MTX+LEF (group-A) using ACR20 guideline (p=0.031).