Background. A successful left ventricular assist device (LVAD) long-term support in an outpatient setting demands that device-related complications are reduced to a minimum. We hypothesized that late onset driveline infections have serious implications on the anticipated application of LVAD as permanent therapy. Methods. Between 1996 and 2005, 73 patients were implanted with the Novacor ( World Heart Corp, Ottawa, Ontario, Canada; n = 35) or the HeartMate ( Thoratec Corp, Pleasanton, CA; n = 38) as either bridge to transplantation ( n = 44) or destination therapy ( n = 29). Our analysis focused on patients with late-onset infection (>= 30 days) of the driveline exit site with prior clinical healing of all incisions. Results. Late driveline infections developed in 17 patients ( 23%) at a median of 158 days ( intraquartile range [ IQR]: 68 to 213 days) after implantation. The median duration of support in this subgroup was 400 days ( IQR, 283 to 849 days). Despite an aggressive treatment algorithm, repeat surgical revision was needed in 12 patients, up to six times in 2 individuals. In 6 patients, the infection progressed to pump pocket infections that led to urgent heart transplantation ( n = 4) or explantation ( n = 2). The individual risk that a driveline infection would develop dramatically increased with the duration of support, reaching 94% at 1 year. Multivariate analysis identified duration of support ( p < 0.001) and documented trauma at the driveline exit site ( p < 0.001) as independent predictors of infection. Number and duration of readmissions to the hospital significantly increased ( p < 0.001), and long-term follow- up for survival ( 4.4 +/- 2.2 years, 100% complete) showed a trend towards impaired outcome after driveline infection ( 5-year survival: 41% versus 70%, p = 0.10). Conclusions. Long-term LVAD support in the current series was jeopardized by late-onset driveline infections, which occurred in all patients with support duration longer than 1 year. Once driveline infections developed, they were difficult to control and significantly increased morbidity.