This prospective study was conducted in rheumatology clinic under the department of medicine of Bangabandhu Sheikh Mujib Medical University from December 2004 to December 2005 to asses the efficacy, safety and compliance of subcutaneous methotrexate (MTX) in active rheumatoid arthritis (RA) patients. A total of 92 active rheumatoid arthritis patients according to American College of Rheumatology (ACR) criteria were recruited for the trial for six months. Among them 46 cases belonged to injectable MTX group and 46 cases belonged to oral MTX group. Mean±SD age of patients was 45.54±12.42 vs. 44.63±13.99 years in subcutaneous group and oral group respectively. In the subcutaneous group 41 were female and 5 male; in the oral group 34 were female and 12 male. Mean duration of the disease was 49.74 months in subcutaneous group and 49 months in oral group. RA test was positive in 35 cases in both groups whereas Rose Waaler test was positive in 19 patients in subcutaneous group and 14 patients in oral group. At 24 week, response rate of ACR 20 was significantly higher in subcutaneous MTX than oral MTX group (93% vs. 80%, p=0.02). Similarly ACR 50 response was significantly higher in subcutaneous MTX than in oral group (89% vs. 72%, p=0.03). ACR 70 response was not significantly higher in SCMTX group then oral group (11% vs. 9 %, p=0.72). Adverse effects were relatively less in subcutaneous MTX and most common side effects were nausea (37% vs. 63%), vomiting (11% vs. 30%), dyspepsia (29% vs. 48%), dizziness (4l% vs. 52%) and alopecia (72% vs. 85%). The results of the study demonstrated that subcutaneous MTX was significantly more effective than oral MTX at the same dosage in active Rheumatoid arthritis patients with no increase in side effects.