Aim of the study is to evaluate the effects of Prostaglandin E-1 (PGE-1) in patients with peripheral arterial disease (PAD) at the 2nd b stage Fontaines classification. The study, controlled, single blinded, enrolled 123 patients with intermittent claudication that were randomised in two groups; the first group received a treatment with PGE-1 while the second one received a pentoxifylline-buflomedil association by venous infusion. We evaluated: Pain Free Walking Distance (PFWD), Maximum Walking Distance (MWD), Rest Flow (RF), Peak Flow (PF), Basal (BVR) and Minimal Vascular Resistance (MVR) with a strain gauge plethysmograph, Resting Flow (RF), Peak Flow (PF), time to reach the Peak Flow (tPF) and time to recovery of the base values (tRF) with laser Doppler flowmeter. After a four weeks treatment, we observed an increase of 370% about PFWD and of 260% in the MWD in patients treated with PGE-1; the other group showed an increase of 110% and 118% respectively. Moreover, the patients of the first group showed a significant increase regarding the plethysmographic Peak Flow (from 9.75±1.37 to 16.21±1.75, p < 0.001), greater than the one observed in the second group (from 9.53±1.41 to 13.47±1.53, p < 0.05); also the laser Doppler parameters showed a significant reduction, more evident in the first group (tPF from 23.0±7.5 to 10.5±4.9, p < 0.001; tRF from 73.5±22.7 to 48.3±13.5, p < 0.001) than in the second one. In conclusion, our study shows the efficacy of PGE-1 in patients with 2nd b stage Fontaine PAD; PGE-1 improves the microcirculation and the haemodynamics in peripheral districts and determines an increase in the pain free walking distance and in maximum walking distance.