Patients in ASSENT-4 PCI undergoing tenecteplase-facilitated percutaneous coronary intervention (PCI) had more adverse events than those undergoing primary PCI. We analysed this to gain further insights. A total of 549 patients with facilitated PCI and 541 undergoing primary PCI were characterized according to the extent of ST resolution. We also examined the relationship between time from symptom onset, presence of baseline Q waves, and 90 day events. Irrespective of treatment, 90 day mortality was lowest among 186 patients with complete ST resolution at both 60 and 180 min (1.8% facilitated; 0% primary PCI group) and highest in those 502 patients without complete ST resolution at either 60 or 180 min (6.7% facilitated; 5.2% primary PCI group, all P < or = 0.05). Patients undergoing facilitated PCI presenting >3 h with baseline Q waves also had higher 90 day mortality compared with those without Q waves (10.4 vs. 2.5%, P = 0.056). No significant differences were found within primary PCI patients on the basis of time from symptom onset or presence of initial Q waves. In this post hoc analysis, our data suggest that a fibrinolysis-facilitated PCI strategy was especially harmful in patients presenting beyond 3 h from symptom onset with established Q waves on their baseline ECG. This may relate to the convergence of later, less effective pre-procedural reperfusion but persisting exposure to the pro-thrombotic and bleeding risks of fibrinolysis.