Cardiac resynchronization therapy (CRT) is a new therapeutic option in patients with heart failure and ventricular conduction delay. We compared the long-term performance of left ventricular (LV) pacing via the coronary venous (CV) approach and a limited lateral thoracotomy (LLT). Data from 81 patients (age 65 +/- 12 years; 52 men, New York Heart Association class 3.0 +/- 0.4, ejection fraction 24 +/- 6%) were retrospectively analyzed for 1 year after implantation of a CRT system. Twenty-five patients received LLT leads and 56 patients received CV leads. Postoperative hospitalization was shorter after CV lead implantation (8 +/- 4 vs 12 +/- 5 days, p <0.01). No significant differences in LV pacing and sensing performance between both approaches were observed after 12 months. Reinterventions were necessary in 7 patients after CV implantation compared with only 1 reintervention (4%) in the LLT group (p = NS). Postoperative chest radiographs revealed an anterior lead position in 11 of 25 patients (44%) in the LLT group versus 3 of 56 patients (5.4%) in the CV group (p = 0.00007). Echocardiographic data demonstrated a significant increase in LV ejection fraction in the CV group (from 26.1 +/- 5.2% to 35.3 +/- 14.3% at 12 months, p <0.001, n = 42) in contrast to the LLT group (from 24.5 +/- 6.2% to 28.5 +/- 7.5% at 12 months, p = NS, n = 16) at 12-month follow-up. Cardiopulmonary exercise testing in 35 patients showed significantly more improvement in peak oxygen consumption after 12 months in the CV group (15.5 +/- 3.1 vs 13.6 +/- 2.6 ml/min/kg at implant, n = 22) compared with the LLT group (12.7 +/- 1.5 vs 11.8 ml/min/kg at implant, n = 13, p = 0.004). At 1-year follow-up the mortality rate was 24% (6 of 25) after LLT lead implantation versus 12.5% (7 of 56) after CV implantation (p = NS). Our data show that the LLT approach for LV lead placement in CRT systems has the advantage of a lower incidence of reinterventions. Hospitalization was longer, increase in functional capacity smaller, and mortality at 1-year follow-up higher, which were potentially related to a more anterior lead position. Therefore, CV leads are preferable to LLT leads.