This study was done to see the efficacy and tolerability of methotrexate and hydroxychloroquine in the Treatment of Rheumatoid Arthritis. It was an open label controlled clinical trial, done in Mymensingh Medical college hospital. Fifty six patients were selected by random sampling method, 28 were included in methotrexate group and another 28 for hydroxychloroquine group using inclusion & exclusion criteria. Primary efficacy variables (DAS28, daily naproxen), secondary efficacy variables, and safety measurement variables studied both clinically & laboratory investigations. The data were analyzed by computer with the help of SPSS. The student's t test was used as test of significant. The mean age of the patients at diagnosis was almost identically distributed between methotrexate and hydroxychloroquine group (41.7±12.2 vs. 42.9±9.2 years, p=0.659). Disease activity at baseline was found to be almost homogeneous to each group except CRP which was observed to be significantly higher in methotrexate group than hydroxychloroquine group (p<0.001). Disease activity at 1 month of treatment reduced in the methotrexate group than those in hydroxychloroquine group (p<0.05 in each case). After 3 and 6 months of treatment, disease activity decreased significantly in both groups (p<0.001 and p<0.05 respectively). The average daily dose of NSAID (Naproxen) decreased significantly (p<0.001). Safety variables at 6 month were within normal physiological ranges and did not differ in groups (p>0.05) indicating that both methotrexate and hydroxychloroquine were effective and safe to use in rheumatoid arthritis. The difference in the incidence of adverse effects, total or individual, was almost nil.