We sought to compare the effects of intracoronary administration of a fibrinolytic drug (tenecteplase) to those of a glycoprotein IIb/IIIa inhibitor (abciximab) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). In this pilot trial, 76 patients (59 male) with anterior STEMI were randomised to intracoronary infusion of reduced-dose tenecteplase or abciximab during PPCI. Angiography was repeated at 48 hours to assess corrected TIMI frame count (cTFC) and TIMI myocardial perfusion grade (TMPG). The primary endpoint was infarct size as assessed by cardiac MRI. The abciximab group showed lower cTFC (median 14.1 [IQR 9.4-17.1]) than the tenecteplase group (18.2 [10.0-28.2]) (p=0.02), and the proportion of patients with TMPG grade 2/3 was higher in the abciximab group (90.3% vs. 67.7%; p=0.03). Major cardiac and cerebrovascular event rates did not differ; however, notably, 2/38 patients in the tenecteplase group experienced subacute stent thrombosis. At four months, there were no significant differences in infarct size between the tenecteplase and abciximab groups (17.0 g [9.6-27.5] vs. 21.1 g [11.3-35.0], p=0.33). Intracoronary administration of tenecteplase did not reduce infarct size compared to abciximab in STEMI patients undergoing PPCI. Tenecteplase exhibited poorer myocardial reperfusion and might be associated with increased subacute stent thrombosis.