Naftidrofuryl has been used for the treatment of intermittent claudication, a symptom of mild to moderate peripheral occlusive arterial disease (POAD), for at least 2 decades. As a serotonin 5-HT2 receptor antagonist, naftidrofuryl has vasoactive properties in addition to its favourable effects on oxidative metabolism, peripheral transcutaneous oxygen pressure and the rheological properties of platelets and erythrocytes. The drug may also reduce hypercholesterolaemia-induced intimal proliferation. Clinical trials which conform best with European guidelines have shown that 3 and 6 months' oral therapy with naftidrofuryl 600 or 633 mg/day (in 3 or 2 divided doses) increased pain-free walking distance to a greater extent than placebo administration in patients with POAD. Surgical revascularisation was required less often during 6 months of therapy with naftidrofuryl than in placebo recipients, confirming the superiority of naftidrofuryl treatment compared with placebo. Available data provide some evidence of efficacy of the drug in the treatment of ischaemic rest pain and vascular ulceration. However, further trials are required before the usefulness of oral naftidrofuryl in severe POAD can be fully established. When given orally, naftidrofuryl is well tolerated. Mild gastrointestinal effects are the most common adverse events, requiring withdrawal of therapy in approximately 1.2% of patients compared with 0.95% of placebo-treated patients. In summary, oral naftidrofuryl improves the symptoms of intermittent claudication in patients with POAD with minimal risk of adverse effects. Therefore, in patients with Fontaine's classification stage II POAD for whom lifestyle modifications and management of concomitant disease have provided insufficient benefit, naftidrofuryl is potentially useful.