Objective This study aimed at exploring access site-related vascular complication rates associated with the use of the vascular closure device (VCD) Angio-Seal™ in an unselected patient population undergoing elective as well as emergency coronary angiography or intervention. Background The VCD Angio-Seal™ is widely used to achieve hemostasis after diagnostic and interventional cardiac procedures. There are only little data on the frequency of vascular complications after the use of the VCD Angio-Seal™ in patients in non-elective settings. Method In-hospital vascular complications were prospectively assessed in 4,653 consecutive cardiac catheterization procedures, which included 2,772 elective diagnostic and 960 elective percutaneous coronary interventions (PCI), and 921 emergency cardiac catheterizations in patients with NSTEMI/STEMI. In 2,077 procedures manual compression (MC) and in 2,576 procedures VCD was applied. Complication rates for manual compression and VCD use were studied and multivariate analyses performed to disclose predictors for access site-related vascular complications. Results Vascular complication rates in patients receiving MC to achieve hemostasis were similar to those receiving a VCD (MC 3.4% vs. VCD 3.2%, p = n.s.). Separate analysis of vascular complication rates for subgroups revealed a significant reduction in vascular complications for the PCI group using a VCD (MC 7.7% vs. VCD 3.2%, p = 0.003). In emergencies VCD use lead to a rise in vascular complications (MC 0.9% vs. VCD 6.3%, p < 0.001). Conclusions In contrast to elective settings, the risk of access site-related vascular complications is significantly increased after application of the VCD Angio-Seal™ in patients undergoing emergency catheterizations for NSTEMI/STEMI compared with manual compression.