Vascular access-site complications are an important cause of morbidity following catheterization procedures. Manual compression is the "gold standard" in achieving hemostasis of an arteriotomy site; however, manual compression is limited by the need to interrupt anticoagulation, prolonged bed rest, patient discomfort and time demands for healthcare providers. Vascular closure devices (VCDs) improve patient comfort, free medical staff resources and shorten the time needed for hemostasis, ambulation and discharge. However, the safety of VCDs remains in question and they may increase the risks of infection and leg ischemia. Compared with manual compression, the rate of major complications appears to be increased with VasoSeal, decreased with Angio-Seal and decreased in diagnostic cases with Perclose. The safety of VCDs cannot be assumed due to "class effect," and nearly all individual trials are underpowered to detect differences in complication rates, so the safety of other individual VCDs is unclear. In the absence of puncture site-related risk factors, VCDs as a whole appear to have little influence on complication rates, and patients at high baseline risk for bleeding due to clinical factors may benefit from these devices. Screening with femoral angiography prior to VCD placement and avoidance of VCDs in the presence of puncture site-related risk factors might reduce the risk of vascular complications. This review describes the mechanism, efficacy and safety of VCDs including hemostasis pads, the FemoStop, Clamp Ease, Mynx, Duett, FISH, Boomerang, ExoSeal, Starclose, VasoSeal, Angio-Seal and Perclose devices.