Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p < 0.001). The AIx for all patients increased from 22.0 +/- 14.0% to 24.6 +/- 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 +/- 23.7% to 141.2 +/- 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.