The aim of this paper was to compare the use of two different commercially available vascular closure devices (VCD), Angioseal VIP® (St. Jude Medical, St. Paul, MN, USA) and StarClose SE (Abbott Laboratories, Abbott Park, IL, USA).From January 2010 to January 2012, 347 patient underwent retrograde femoral arterial puncture for different interventional procedures (angioplasty, stenting, embolization for bleeding, fibrinolysis for ischemia and chemoembolization). Hemostasis was achieved by deployment of an Angioseal VIP® (N.=184) or StarClose SE® (N.=163). In 94 cases, the retrograde femoral access was bilateral and managed with two StarClose SE devices (N.=53) or an Angioseal VIP® plus a StarClose SE® (N.=41).Technical success was obtained in 95.1% (330/347) of patients. Overall time to hemostasis (TTH) and time to ambulation (TTA) were 5,5±1,5 min (range 3-8 min) and 6±2.5 hr (range 2-9 hours) respectively. No statistical significative difference (P>0.05) were appreciable between to groups for both TTH and TTA: Angioseal VIP® TTH was 5.3±1.4 min and StarClose SE® TTH was 5.6±1.6 min; Angioseal VIP® TTA was 5.9±1.8 hr and StarClose SE® TTA was 6.1±1.9 hr. VAS scores result underline a mild difference between two devices. Angioseal VIP® patients experience a mild to moderate pain within the first 3 minutes from the deployment. Whereas StarClose SE® patients still experience pain at 5 minutes from deployment. The device failure rate was 4.9% (17 cases) and included 13 minor complications and 4 major complications. Minor complications (3.75%) occurred during the initial phase and consisted in recurrent wound bleeding (N.=5 StarClose SE®; N.=4 Angioseal VIP®) treated with manual compression, and hematoma (N.=2 StarClose SE®; N.=2 Angioseal VIP®) that solved spontaneously. The 4 major complications (1,15%) were: 1 Angioseal-related common femoral artery (CFA) obstruction treated with surgical bypass from the CFA to the superficial femoral artery; 1 Angioseal-related CFA dissection solved with surgery; 1 Angioseal-related embolization of the deep femoral artery partially treated with localized fibrinolysis; 1 StarClose-related pseudoaneurysm treated with manual compression.Both Angioseal VIP® and StarClose SE® systems can be considered safe and effective in providing hemostasis following a variety of interventional vascular procedures.