Objective: Serum IGF-binding protein 2 (IGFBP2) concentrations are reduced in obese humans and increase after a prolonged period of fasting. We investigated the association between IGFBP2 levels and mortality together with other factors that are related to IGFBP2, including the metabolic syndrome and physical function. Design: A prospective observational study at a clinical research center of 403 independently living elderly men (aged 73-94 years). Methods: Mortality was registered during 8.6 years of follow-up. Physical performance score (PPS), grip strength (GS), and bone mineral density (BMD) were measured. The measurements taken a baseline were: IGF1; IGFBP1, -2, and -3; IGF1 bioactivity; triiodothyronine (T-3); and reverse T-3. Further, BMI, insulin sensitivity, cholesterol, inflammatory markers, and albumin levels were also measured. Results: During the follow-up, 180 men died. Higher PPS, GS, and BMD were independently related to a reduced mortality (hazard ratio (HR)=0.87/point, 95% confidence interval (95% CI)=0.82-0.91, P<0.001; HR=0.96/kp, 95% CI 0.94-0.98, P<0.001; and HR=0.21/(g/cm(2)), 95% CI 0.07-0.61, P<0.01). Higher serum IGFBP2 levels were strongly related to mortality (HR=2.26/(mg/l), 95% CI 1.57-3.27, P<0.001). This was independent of comorbidity, physical function, IGF1 bioactivity, and other somatotropic para Conclusion: Despite the strong relationship between high IGFBP2 and low physical function, both were strongly and independently related to increased 8-year mortality in elderly men. IGFBP2 may be a useful biomarker integrating the nutritional status, as well as the biological effects of GH, IGF1, and insulin.