Prostaglandin E1 (PGE1) is widely used in the treatment of limb ischemia for its potent vasodilatory and antiplatelet effects. In order to assess the curative effect of liposomal PGE1 (lipo-PGE1) as an adjuvant to surgery in patients with acute lower limb ischemia (ALLI), 204 patients who underwent hybrid procedures (operative thromboembolectomy or bypass and necessary endovascular interventions) for ALLI were randomly divided into a blank control group and a lipo-PGE1 group (intravenous infusion of 20 μg/day for 12–14 consecutive days following surgery). Patients were followed-up for 6 months after surgical revascularization for clinical events. The primary study endpoint, which was the combined incidence of perioperative (30 days) mortality (POM) and major adverse limb events (MALE; amputation or major intervention), was significantly reduced in patients treated with lipo-PGE1 (5.1% compared with 13.2% in the control group). The overall incidence of clinical events, including POM, MALE and major adverse cardiovascular events, was significantly reduced in patients receiving lipo-PGE1 (8.2%) compared with the controls (20.8%). Hybrid procedures are an improved method for treating ALLI and may remedy underlying lesions of vessels following thromboembolectomy.