Primary percutaneous coronary intervention (PCI) is more effective than fibrinolytic therapy for ST-segment elevation acute myocardial infarction (STEMI), but time to intervention can be considerable. Our aim was to investigate whether the administration of full-dose tenecteplase before a delayed PCI could mitigate the negative effect of this delay. We did a randomised study in which we assigned patients with STEMI of less than 6 h duration (scheduled to undergo primary PCI with an anticipated delay of 1-3 h) to standard PCI (n=838) or PCI preceded by administration of full-dose tenecteplase (n=829). All patients received aspirin and a bolus, without an infusion, of unfractionated heparin. Our primary endpoint was death or congestive heart failure or shock within 90 days. Analyses were by intention to treat. This study is registered with , number NCT00168792. We planned to enroll 4000 patients, but early cessation of enrollment was recommended by the data and safety monitoring board because of a higher in-hospital mortality in the facilitated than in the standard PCI group (6% [43 of 664] vs 3% [22 of 656], p=0.0105). Of those enrolled, six were lost to follow-up in the facilitated PCI group and seven in the other group. Median time from randomisation to first balloon inflation was similar in both groups. The median time from bolus tenecteplase to first balloon inflation was 104 min. We noted the primary endpoint in 19% (151 of 810) of patients assigned facilitated PCI versus 13% (110 of 819) of those randomised to primary PCI (relative risk 1.39, 95% CI 1.11-1.74; p=0.0045). During hospital stay, significantly more strokes (1.8% [15 of 829] vs 0, p<0.0001), but not major non-cerebral bleeding complications (6% [46 of 829] vs 4% [37 of 838], p=0.3118), were reported in patients assigned facilitated rather than standard PCI. We also noted more ischaemic cardiac complications, such as reinfarction (6% [49 of 805] vs 4% [30 of 820], p=0.0279) or repeat target vessel revascularisation (7% [53 of 805] vs 3% [28 of 818], p=0.0041) within 90 days in this study group. A strategy of full-dose tenecteplase with antithrombotic co-therapy, as used in this study and preceding PCI by 1-3 h, was associated with more major adverse events than PCI alone in STEMI and cannot be recommended.