Objective: This study was performed to evaluate the feasibility and safety of early sheath removal after percutaneous coronary intervention (PCI) using a locally designed Assiut Femoral Compression Device (AFCD2) vs. manual compression (MC). Background: Due to antithrombotic therapy before, during, and after PCI, the arterial femoral sheath is generally not removed early after PCI. Patients and methods: This was a randomized, controlled trial. We enrolled all patients undergoing PCI at Assiut University Hospitals from September, 2013 to December, 2013. At the end of PCI, the arterial hemostasis method was randomly assigned 1:1 to AFCD2 vs. MC. The sheaths were removed 2 h after PCI, instead of conventional 6 h, in the AFCD2 arm. Results: The trial assigned 100 patients (mean age 57 ± 9 years, 75% men) to AFCD2 (n = 50) vs. MC (n = 50). Both groups were comparable regarding baseline characteristics. Concerning the primary effectiveness end point, there was significantly shorter mean time-to-ambulation with AFCD2 (8.2 ± 1.42 h) vs. MC (12.02 ± 0.22 h; p = <0.001). This was directly reflected on shorter time for hospital discharge eligibility in AFCD2 (11 ± 1 h) vs. MC (15 ± 1 h; p = <0.001). As regards safety, none of our research population experienced major adverse events. The use of AFCD2 was associated with similar occurrence of minor complications, mainly ecchymosis and oozing, compared with MC.