Patients with rheumatoid arthritis (RA) experience excess cardiovascular disease (CVD). We investigated the effects of disease-modifying antirheumatic drugs (DMARD) and dietary intervention on CVD risk in inflammatory arthritis. Twenty-two patients (17 women; 15 with RA and seven with spondyloarthropathy) who were insulin resistant (n = 20), as determined by the Homeostasis Model Assessment, and/or were dyslipidemic (n = 11) were identified. During the third month after initiation of DMARD therapy, body weight, C-reactive protein (CRP), insulin resistance, and lipids were re-evaluated. Results are expressed as median (interquartile range). DMARD therapy together with dietary intervention was associated with weight loss of 4 kg (0-6.5 kg), a decrease in CRP of 14% (6-36%; P < 0.006), and a reduction in insulin resistance of 36% (26-61%; P < 0.006). Diet compliers (n = 15) experienced decreases of 10% (0-20%) and 3% (0-9%) in total and low-density lipoprotein cholesterol, respectively, as compared with increases of 9% (6-20%; P < 0.05) and 3% (0-9%; P < 0.05) in diet noncompliers. Patients on methotrexate (n = 14) experienced a reduction in CRP of 27 mg/l (6-83 mg/l), as compared with a decrease of 10 mg/l (3.4-13 mg/l; P = 0.04) in patients not on methotrexate. Improved cardiovascular risk with DMARD therapy includes a reduction in insulin resistance. Methotrexate use in RA may improve CVD risk through a marked suppression of the acute phase response. Dietary intervention prevented the increase in total and low-density lipoprotein cholesterol upon acute phase response suppression.