OBJECTIVE To assess the efficacy and safety of doxycycline as a disease modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA) and compare it with methotrexate, a standard DMARD. METHODS A single (assessor) blind prospective study with 15 patients of RA randomized to doxycycline and 14 to methotrexate. Baseline disease characteristics were similar in both groups. RESULTS All disease activity measures studied viz. tender and swollen joint counts, physician and patient global assessment, visual analogue pain scale, health assessment questionnaire and ESR improved in both the treatment groups after six months of treatment. The difference between doxycycline and methotrexate was not statistically significant. No major side effects necessitating drug withdrawal were reported from either group. The side effects were few and mostly gastrointestinal. CONCLUSIONS Doxycycline is a safe disease modifying drug in RA whose effect is sustained at six months. It compared favourably with methotrexate over a six month follow up.