Given the accumulating evidence that gamma-glutamyltransferase (␥-GT) is not merely a sensitive marker for liver and bile disorders but also a risk marker for a multiplicity of other chronic diseases, ␥-GT may represent a promising risk indicator for occupational disability, which has emerged as an important public health problem. The association between ␥-GT and disability pension was examined in a cohort of 16,520 male construction workers in Württemberg, Germany, who participated in routine occupational health examinations from 1986 to 1992 and who were followed until 2005. Using the Cox proportional hazards model, hazard ratios were calculated with ␥-GT concentrations in the lowest quartile (1 to 24 U/L) as reference category after adjustment for age and further adjustment for potential confounding factors such as nationality, type of occupation, smoking, alcohol consumption, cholesterol, and body mass index (BMI). Overall, a monotonically increasing association of ␥-GT with all-cause disability pension (total number: n ؍ 2,998 cases) was observed, with the steepest increase at lower levels of ␥-GT. Particularly strong associations were observed for participants in the highest quartile (>67 U/L) and disability pension due to musculoskeletal disorders, diseases of the digestive system, and cardiovascular as well as mental diseases (age-adjusted hazard ratios with 95% confidence intervals: 1.53, 1.27-1.85; 9.68, 3.10-30.21; 1.76, 1.28-2.42; and 1.83, 1.23-2.72, respectively). Conclusion: ␥-GT is a strong risk indicator of all-cause occupational disability even at levels of ␥-GT in the "normal range" and is in particular associated with disability pension due to diseases of the digestive system, musculoskeletal disorders, cardiovascular, and mental diseases. (HEPATOLOGY 2010; 51:482-490.)