Coronary perforation is a rare, but potentially catastrophic complication of percutaneous coronary intervention. It rarely results in cardiac tamponade with the use of standard anticoagulant regimens. But spontaneous cardiac tamponade was reported recently during balloon angioplasty under the large dose of heparin infusion, and after stent implantation under powerful antiplatelet therapy including platelet IIb/IIIa receptor inhibitor administration. We report a case of delayed cardiac tamponade complicated by guidewire manipulation under powerful anticoagulant and antiplatelet therapy, which recurred early after the first pericardiocentesis.