We have examined our prospectively collected experience with femoral artery closure devices. Vasoseal (n = 937), Angioseal (N-742), and Techstar (n = 1001) were utilized consecutively in our laboratory for diagnostic and interventional femoral artery closures. Complications were compared to a similar number of closures with manual compression (MC; n = 1019) before closure devices were utilized. The incidence of surgical repair, acute femoral closure, transfusion due to groin complications, readmission for groin complications, infection, and total complications were examined. We found that the Vasoseal and Angioseal devices were associated with higher rates of total complications than manual compression. The Techstar and manual compression had similar total complication rates. Acute femoral artery occlusion was a potentially serious complication with the Angioseal device. Groin infection occurred with each of the closure devices but not with manual compression.