The aim was to look at the effect of sulodexide in diabetic and non-diabetic patients with peripheral occlusive arterial disease (POAD), by verifying, through meta-analysis of Italian data, if the drug affects the clinical course of claudication or the main risk factors for POAD. Sulodexide increases the pain-free walking distance (benefit 36% vs controls, P < 0.001). The meta-analysis confirmed the effectiveness of sulodexide in improving claudication (lower limit of the 95% CI for overall odds ratio always > 1). There was a marked effect in lowering triglycerides (overall -28%, P = 0.0015), fibrinogen (-13%, P < 0.0001) and plasma and serum viscosities, and in increasing high-density-lipoprotein cholesterol (24.4%, P = 0.0007). The medium-term administration of sulodexide has a therapeutic effect on claudication of diabetic and/or hyperlipidaemic patients suffering from POAD stages- and also counteracts several POAD risk factors. Long-term use of sulodexide appears to be well tolerated. The treatment has a low daily cost; therefore, it has a favourable cost-benefit ratio, in view of the high general costs associated with global POAD care, particularly in diabetic patients.