Aims: To evaluate efficacy and safety of drugs in patients of rheumatoid arthritis (RA) and their impact on quality of life. Materials and Methods: Newly diagnosed patients of RA were included in the study [Group A=Methotrexate (7.5 to 25 mg) orally + Hydroxychloroquine (200 mg) orally& Group B =Methotrexate (7.5 to 25 mg) orally + Hydroxychloroquine (200 mg) orally + Prednisolone (1 mg/kg/day and then tapered to maintenance dose 7.5 mg/day) orally] and followed up for a period of 6 months after enrolment. Efficacy of drugs was assessed using Disability Assessment Score 28 (DAS 28) and Quality of life was measured with Modified Health Assessment Questionnaire (MHAQ).The data was recorded in Microsoft Excel Worksheet version 2007 and statistical evaluation was done using ANNOVA test and unpaired t-test and P<0.05 was considered to be statistically significant. Result: Total 82 patients were included and divided in group [A (n=47) and B (n=35)]. In group A & B, there was significant reduction (P<0.001) in DAS28 at 2nd follow up as compared to baseline. In group B, DAS28 was significantly reduced at 1st follow up (P<0.05). Mean difference between group A & B was non-significant. In group A, total MHAQ was significantly change (P<0.001) at 2nd follow up as compared to baseline. In group B, the groups. Conclusion: MHAQ score was significantly reduced (P<0.001) at 1st follow up and at 2nd follow upas compared to baseline. Significant reduction (P<0.001) in MHAQ observed in both the group at 2nd follow up as compared to 1st follow up. In group B, there was strong correlation (r value=0.7) between DAS28 & MHAQ. Adverse drug reaction observed were mild in severity in both DMARDs decrease the severity of symptoms in RA patients over a period of time but symptomatic improvement is seen earlier in combination of DMARDs (methotrexate and hydroxychloroquine) plus prednisolone therapy.