Depression is common in rheumatoid arthritis (RA) patients, exacerbates disease activity, and may decrease response to first-line disease-modifying antirheumatic drugs. This study aimed to determine if depression affects disease activity among Veterans with early RA prescribed methotrexate (MTX).Participants included Veterans enrolled in the Veterans Affairs Rheumatoid Arthritis registry with early RA (onset < 2 years) prescribed MTX. Depression was assessed at enrollment using International Classification of Diseases codes (296.2-296.39, 300.4, 311). Disease activity was measured using the 28 joint count disease activity score (DAS-28) and other core measures of RA disease activity. Propensity score weights were used to adjust depressed (n=48) and non-depressed (n=220) patients on baseline confounders within imputed datasets. Weighted estimating equations were used to assess standardized mean differences in disease activity between depressed and non-depressed patients at six months and one- and two-years follow-up.The analytic sample was composed of 268 Veterans with early RA prescribed MTX who were predominantly male (n=239; 89.2%) and older (62.7 years ± 10.6) than general population RA patients. Adjusted estimates indicated that depression was associated with significantly higher DAS-28 at six months (β=0.345; 95% CI: 0.007, 0.682) but not at one- or two-years follow-up. Also, depression was associated with significantly worse pain at six months (β=0.385; 95% CI: 0.040, 0.730) and one-year (β=0.396; 95% CI: 0.042, 0.750) follow-up.In early RA, depression is associated with greater short-term disease activity during MTX treatment, as well as more persistent and severe pain.