Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest 99mTc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf 99mTc-sestamibi uptake, in comparison with baseline values (P<0.001); (b) the absence of statistically significant modifications of Doppler blood flow indices of the lower limbs. In conclusion, after chronic administration of PLC, a significant increment in skeletal muscle uptake of 99mTc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics.