The aim of this study was to compare the effectiveness of different disease-modifying anti-rheumatic drugs (DMARDs) in improving disease activity and functional status in patients with rheumatoid arthritis (RA). One hundred and fifty-two Thai RA patients treated with at least one DMARD were enrolled in this 1-year cohort. Demographic characteristics, baseline and end-of-study data on disease activity and Health Assessment Questionnaire (HAQ) Disability Index of the subjects were compared among different DMARD options. Predictors of HAQ score were investigated using regression analysis. The results showed that the studied patients had established RA with mild to moderate activity. More than 85% were prescribed methotrexate (MTX) as single or combined DMARDs. At 1 year, improvement in most activity measures was experienced. However, all patients had functional declines. Patients taking antimalarial agents had the maximal rate of functional deterioration. Patients taking MTX-based DMARDs had significantly lower rate of functional decline than patients taking DMARDs without MTX (p=0.018). Only patients receiving MTX-based DMARDs had clinically meaningful improvement in HAQ score. The predictors of HAQ score at 1 year included baseline HAQ score and patient global assessment at end of study. In conclusion, although DMARD treatment was shown to improve disease activity in RA patients, functional deterioration was evident in our cohort. Thus, measures of functional status are more appropriate than measures of disease activity to evaluate treatment effects of DMARDs in established RA in clinical practice. MTX-based DMARDs should be prescribed where possible in RA patients with persisting activity due to their ability to delay functional deterioration.