OBJECTIVES: Drugs used for the treatment of rheumatoid arthritis (RA) have the potential to affect cardiovascular risk factors. There is concern that corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors could affect cardiovascular risk adversely, while drugs such as the antimalarial, hydroxychloroquine, may have beneficial effects. However, there is limited information about cardiovascular risk factors in patients with RA receiving different drugs. METHODS: We measured cardiovascular risk factors including systolic and diastolic blood pressure, serum HDL and LDL cholesterol, glucose and homocysteine concentrations and urinary F(2)-isoprostane excretion in 169 patients with RA. Risk factors were compared according to current use of corticosteroids, methotrexate, antimalarials, NSAIDs, COX-2 inhibitors, leflunomide and TNF-alpha blockers. Comparisons were adjusted for age, sex, race, disease activity (DAS28 score), current hypertension, diabetes, smoking status and statin use. RESULTS: No cardiovascular risk factor differed significantly among current users and non-users of NSAIDs, COX-2 inhibitors, methotrexate and TNF-alpha blockers. Serum HDL cholesterol concentrations were significantly higher in patients currently receiving corticosteroids (42.2 +/- 10.5 vs. 50.2 +/- 15.3 mg/dL, adjusted P < 0.001). Diastolic blood pressure (75.9 +/- 11.2 vs. 72.0 +/- 9.1 mm Hg, adjusted P = 0.02), serum LDL cholesterol (115.6 +/- 34.7 vs. 103.7 +/- 27.8 mg/dL, adjusted P = 0.03) and triglyceride concentrations (157.7 +/- 202.6 vs. 105.5 +/- 50.5 mg/dL, adjusted P = 0.03) were significantly lower in patients taking antimalarial drugs. Plasma glucose was significantly lower in current lefunomide users (93.0 +/- 19.2 vs. 83.6 +/- 13.4 mg/dL, adjusted P = 0.006). CONCLUSIONS: In a cross-sectional setting drugs used to treat RA did not have major adverse effects on cardiovascular risk factors and use of antimalarials was associated with beneficial lipid profiles.