Propionyl-L-carnitine stimulates energy production in ischaemic muscles by increasing citric acid cycle flux and stimulating pyruvate dehydrogenase activity. The free radical scavenging activity of the drug may also be beneficial. Propionyl-L-carnitine improves coagulative fibrinolytic homeostasis in vasal endothelium and positively affects blood viscosity. Improvements in maximum walking distance (MWD) correlated positively with increased mitochondrial oxidative adenosine triphosphate (ATP) synthesis in a study in patients with peripheral arterial disease. Oral propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD compared with placebo in patients with peripheral arterial obstructive disease (Fontaine Leriche stage II) in double-blind multicentre phase III studies (mean improvements ranged from 21 to 50% with placebo and from 33 to 73% with propionyl-L-carnitine). In one phase III study, propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD (measured by treadmill) compared with placebo (by 73 vs 46% after 24 weeks) in patients with intermittent claudication. Oral propionyl-L-carnitine therapy was associated with significant improvements in quality of life compared with placebo in patients with a baseline MWD < 250m. Propionyl-L-carnitine appears to be well tolerated, showing a similar incidence of adverse events to that reported in placebo recipients.