The effect of the prostaglandin I2 analog, beraprost sodium (BPS), on hemodialysis (HD) patients with peripheral arterial disease (PAD) has not been fully elucidated. The effect of BPS was compared to that of PAD drugs in HD patients with PAD in a multicenter randomized prospective interventional pilot study (J-PADD). Seventy-two PAD patients on HD were entered and randomly divided into two groups; that is, BPS group (Group A: n = 35) and PAD drug (cilostazol or sarpogrelate) group (Group B: n = 37). Primary endpoint was changes in skin perfusion pressure (SPP). Kidney Disease Quality of Life (KDQOL) score, cardiovascular events, PAD events, and adverse events were also evaluated. SPP increased significantly in both groups at 24 weeks from their basal levels. The absolute increase of SPP in Group A and Group B were 15.4 ± 30.0 mm Hg (P < 0.0001) and 20.2 ± 22.1 mm Hg (P = 0.025) (instep), and 13.8 ± 19.3 mm Hg (P < 0.0001) and 9.2 ± 16.3 mm Hg (P = 0.041) (sole), respectively. Changes of KDQOL score showed significantly better result in the role of physical score in Group A compared with Group B. Although heart rate was unchanged in Group A, 9.3/min increase was seen in Group B patients who received cilostazol. There was no intergroup difference in cardiovascular events and/or PAD events between the two groups during the study period. This exploratory pilot study suggested BPS was as effective as anti-platelet drugs in improving microcirculation in HD patients.