To assess the association of circulating concentrations of angiopoietin‐2 (Ang‐2) and its soluble receptor Tie‐2 (sTie‐2) with all‐cause, cardiovascular, and cancer mortality in a population‐based sample.

Angiopoietin‐2 and sTie‐2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow‐up of 6.2 years, 217 participants died. Ang‐2 levels were positively associated with all‐cause mortality [HR 1.29; 95% confidence interval (CI) 1.19–1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18–1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89–1.32; P = 0.416). Levels of sTie‐2 were not significantly related to all‐cause mortality (HR 1.12; 95% CI 0.98–1.27; P = 0.102). Adding Ang‐2 to a prediction model for all‐cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, −0.015; P = 0.571).

In our community‐based sample, higher serum Ang‐2 concentrations were associated with greater risk for all‐cause and cardiovascular mortality, suggesting that subtle increases in Ang‐2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang‐2 to a mortality prediction model only modestly improved discrimination.