To prospectively assess the incidence and clinical significance of thromboembolic complications in patients with multiple (> or = 3) noninfected transvenous leads; 48 consecutive patients were evaluated. Half of the patients had two ventricular leads and one atrial lead, 15 patients had two atrial leads and one ventricular lead, while 9 patients had two ventricular and two atrial leads. No additional care was provided except for aspirin (80 mg bid) and annually performed echo-Doppler studies. Clinical follow-up included signs and symptoms of subclavian and/or axillary vein thrombosis, the presence of right congestive heart failure, the number of hospital admissions, and death. Echo-Doppler studies assessed the presence of an enlarged right atrium or ventricle, right atrial or ventricular spontaneous contrast, and the presence of tricuspid regurgitation. During a total follow-up of 7.4 +/- 2.2 years there were no differences in the incidence of clinical variables as compared to age-matched controls with DDD pacemakers. The most common complication was transient venous thrombosis (mostly presenting as venous prominence 1-2 weeks after implantation), which was seen in 17% of the study group versus 15% in controls (NS). Cumulative mortality was not different in both groups (13% in the study group vs 15% in controls). No differences were present with respect to hospital admissions (1.1 +/- 0.27/year in the study group vs 1.2 +/- 0.30/year in the controls). In patients with multiple ventricular leads, tricuspid regurgitation on echo-Doppler studies was more frequent (24%) as compared to controls (4%); however, clinical signs of right heart failure were equally distributed. Thus, patients with multiple (> or = 3) noninfected leads have no clinical adverse outcome during long-term follow-up.