Increased cardiovascular morbidity and mortality in rheumatoid arthritis (RA) patients cannot be entirely explained by traditional risk factors, suggesting that systemic inflammation characterizing this disease may accelerate atherosclerosis. Technetium 99m-Methoxyisobutyl isonitrile (Tc-99m sestamibi) is a myocardial perfusion imaging agent that has been suggested for evaluation of peripheral vascular disease. We used Tc-99m sestamibi muscle scan to investigate the prevalence of preclinical atherosclerosis in RA patients by perfusion reserve (PR) measurement. This study included 25 RA patients and 25 controls; 13/25 RA (GII) were on glucocorticoids and 12/25 (GI) were not. Database included full history, clinical examination, relevant laboratory tests, and Tc-99m sestamibi muscle scan for lower limbs. The percentage increase in the total counts (Cts) in the exercising calf termed PR was calculated according to the formula: (PR %) = (Cts in exercising calf-Cts in resting calf) ÷ (Cts in resting calf) × 100%. A significant difference was found between the means of PR in RA and controls (30.7±22.6% vs. 48.3±27.2%, P = 0.015). The mean perfusion reserve of GII correlated significantly with the steroids cumulative dose (P = 0.01). A statistically significant negative correlation was elicited between PR and disease duration (P = 0.024), while the negative correlation between PR and Disease Activity Index (DAS28) was not statistically significant (P = 0.065). Tc-99m sestamibi lower-limb muscle scan could be a useful screening tool for detection of preclinical atherosclerosis in lower limbs of RA patients, so early prophylactic measures and therapy modifications could be considered.