This study assesses the feasibility and safety of immediate sheath removal after coronary angioplasty with the use of 6 French (Fr) guiding catheters by the femoral route and weight-adjusted low-dose heparin (100 IU/kg). We prospectively evaluated such a strategy among a single-center cohort of 261 consecutive patients undergoing routine percutaneous transluminal coronary angioplasty (PTCA). Immediate sheath withdrawal was performed in cases when post-PTCA residual coronary stenosis was less than 30%, with or without stenting. One hundred eighty-two (70%) of the enrolled patients were eligible for immediate sheath removal. When compared with non-eligible patients (sheath removal 4 hours or more post-PTCA), we observed a reduction of hematoma occurrence (15% vs. 30%; p < 0.01), time to manual hemostasis of the puncture site (13.8 +/- 7 vs. 19.7 +/- 12 minutes; p < 0.0001), and time to hospital discharge (2.2 +/- 1.9 vs. 2.8 +/- 1.8 days; p < 0.02), while ischemic event rate was similar (1 vs. 2 non-Q wave myocardial infarction; 2 vs. 1 repeat PTCA for out-of-lab acute vessel closure). In conclusion, a good angiographic result at completion of PTCA using a 6 Fr sheath, even without stenting, makes an immediate sheath removal feasible at no increased risk and with a potential reduction in minor bleeding complications.