Objective: This study was aimed to investigate the acute effect of PTCA on clotting activation and fibrinolytic system and the possible role of modifications of haemostasis in relation to restenosis-related clinical recurrence after PTCA. Setting: Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy. Material and methods: In 83 unselected patients (70 men and 13 women) undergoing PTCA, blood clotting (fibrinogen, F1+2 TAT) and fibrinolytic activation (D-dimer, ELT, PAI-1, t-PA) were assayed before and immediately after PTCA. Results: At the end of the procedure there was a significant decrease in plasma levels of fibrinogen ( P < 0.0001), F1+2 ( P < 0.0001), TAT ( P < 0.0001), PAI-1 ( P < 0.0001) and t-PA ( P < 0.001), a shortening of ELT ( P < 0.0001) and a significant increase in D-dimer concentration ( P < 0.0005). Post-procedyral PAI-1 activity levels were significantly higher in patients with subsequent clinical recurrence owing to restenosis than in those without ( P < 0.0005); similarly, patients with restenosis showed lower t-PA levels ( P < 0.0005) and longer ELT ( P < 0.05) after PTCA than those without. An earlier occurrence of clinical recurrence owing to restenosis was observed in patients with an increase or no variation of PAI-1 levels at the end of the procedure. Conclusion: These results suggest that the early fibrinolytic response to balloon injury is a relevant determinant of the risk of clinical recurrence owing to restenosis after PTCA, possibly by determining ‘per se’ a longer local persistence of thrombus and by triggering a release of mediators involved in the proliferation of smooth muscle cells.