Abstract： Objective To compare the effects of upstream versus downstream tirofiban on tissure level perfu-sion and troponin Ⅰ release in high-risk non-ST-segment elevation acute coronary patients treated with percutaneous coronary intervention. Methods We randomized 138 non-ST-segment elevation acute coronary syndrome patients un-dergoing PCI to receive upstream(in the coronary care unit) and downstream(just prior to PCI) tirofiban. We com-pared the effects between the two drug regimens on tissue-level peffusion using Thrombolysis In Mycardial Infarction (TIMI) fram count,the TIMI myocardial perfusion grade(TMPG) and cardiac tropinin Ⅰ (cTn Ⅰ) release before and after PCI. Results There was no significant difference between two groups in TIMI 3 flow(P>0.05). High percent-age of TMPG 3 perfusion were observed in upstream tirofiban group than in downstream tirofiban group (P < 0.05). Post-procedual cTnI elevation was significantly less frequent among patients in the upstream group (P < 0.05). The cTnI level after PCI was significantly lower with upstream tirofiban compared with downstream tirofiban group (P<0.05). Conclusion Among high-risk non-ST-segment elevation ACS patients treated with an early invasive strategy, upstream tirofiban is associated with improved tissue-level perfusion and attenuated myocardial damage.