The obesity paradox has recently attracted considerable interest in the study of many diseases. In this investigation we examine the relationship between body mass index (BMI) and prognosis after left ventricular assist system (LVAS) implantation. We measured the BMI of 64 patients 3 months after LVAS implantation for end-stage heart failure. The patients were classified according to BMI into Group A (BMI <16 kg/m(2)), Group B (BMI 16 to 18.4 kg/m(2)) or Group C (BMI > or =18.5 kg/m(2)). We compared the prognosis among these three groups after a mean follow-up period of 583 days. Seven patients were weaned from their LVAS, 24 received heart transplantation, 25 died on the transplant waiting list, and 8 remain on the list. Long-term (>1 year) mortality was significantly higher in Group A than in Groups B and C (59% vs 40% and 18%, respectively; p < 0.05). The incidence of sepsis was also significantly higher in Group A than in Groups B and C (68% vs 45% and 32%, respectively; p < 0.05). After multivariate adjustment, BMI <16 kg/m(2) (hazard ratio HR 14.9; 95% confidence interval CI 2.61 to 86.0; p < 0.01) and levels of C-reactive protein (HR 1.56; 95% CI 1.15 to 2.13; p < 0.01) were independent predictors of mortality. A lower BMI indicated a poor prognosis, as well as a higher incidence of a fatal complication, sepsis, after LVAS implantation. Control of BMI could be an effective way to improve management of patients with LVAS.