Background: This study was conducted to determine the effect of a disease-management model termed an "intensive surveillance protocol" (ISP) on survival in ventricular assist device (VAD) patients. This intervention consisted of a formalized, protocol-driven, multi-disciplinary team approach to VAD patient follow-up initiated August 1, 2006. The goal was to attain an internal program benchmark of 70% survival at 2 years. Historically, 2-year survival after VAD implant has been sub-optimal, and no patient management algorithms have been formally tested to determine their effect on 2-year survival. Methods: The study comprised 76 patients, of whom 26 had a VAD as destination therapy (DT) and 50 as a bridge to transplant (BTT), from July 1, 2003, to June 30, 2008. Survival before and after initiation of ISP was compared. A parametric hazard multivariable analysis, with a time-varying covariable for implementation of ISP, was used to evaluate of other factors affecting survival. Results: Survival at 16 months was 100% for DT patients who received a VAD after August 1, 2006 vs 64% for the earlier era (p = 0.06). For BTT, 16- month survival was 71% vs 43% (p = 0.03). Predicted 2-year survival before and after implementation of the ISP improved from 30% to 87% for DT (p = 0.02) and from 20% to 61% for BTT patients (p = 0.01). Predictors of midterm survival by multivariable analysis included ISP (p = 0.004), younger age (p = 0.03), non-emergent implant (p < 0.0001), and isolated left ventricular VAD (p < 0.0001). After adjustment for covariables, the ISP was associated with a 70% reduction in the hazard for death for the entire cohort (p = 0.004). The effect of ISP was also significant in the patients who received the HeartMate XVE (Thoratec, Pleasanton, CA), which spanned both eras of the study. Conclusions: Survival improved for DT and BTT VAD patients after implementation of the ISP, with a dramatic decrease in hazard for death. Although the transition from pulsatile to axial flow technology occurred during the study period and likely contributed to improved outcomes, the institution of the ISP provided an important and significant contribution to improved survival through a proactive approach to patient management, allowing earlier identification of potential adverse events. For optimal outcomes, VAD patients require intensive follow-up surveillance protocols that have previously become standard in the care of heart transplant patients. © 2011 International Society for Heart and Lung Transplantation.