Background-Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Methods and Results-Two hundred forty-two consecutive patients undergoing elective PCI with undetectable preprocedural cTnI were recruited. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an uninflated cuff around the arm) before arrival in the catheter laboratory. The primary outcome was cTnI at 24 hours after PCI. Secondary outcomes included renal dysfunction and major adverse cardiac and cerebral event rate at 6 months. The median cTnI at 24 hours after PCI was lower in the remote IPC compared with the control group (0.06 versus 0.16 ng/mL; Pϭ0.040). After remote IPC, cTnI was Ͻ0.04 ng/mL in 44 patients (42%) compared with 24 in the control group (24%; Pϭ0.01). Subjects who received remote IPC experienced less chest discomfort (Pϭ0.0006) and ECG ST-segment deviation (Pϭ0.005) than control subjects. At 6 months, the major adverse cardiac and cerebral event rate was lower in the remote IPC group (4 versus 13 events; Pϭ0.018). Conclusion-Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events. (Circulation. 2009;119:820-827.)