Low serum 25-hydroxyvitamin D (25(OH)D) and elevated parathyroid hormone (PTH) levels have been linked to insulin resistance, the metabolic syndrome (MetS) and its components. Data in healthy, community-dwelling Europeans are lacking, and previous studies have not excluded subjects receiving drug treatments that may distort the relationship between 25(OH)D/PTH and MetS. The aim of our analysis was to examine the association of 25(OH)D and PTH with Adult Treatment Panel III-defined MetS in middle-aged and older European men. This was a population-based, cross-sectional study of 3369 men aged 40-79 years enrolled in the European Male Ageing Study. After exclusion of subjects with missing data, 3069 men with a mean (+/-s.d.) age of 60+/-11 years were included in the analysis. Age-adjusted 25(OH)D levels were inversely associated with waist circumference, systolic blood pressure (BP), triglycerides, and glucose (all P<0.01). Age-adjusted PTH levels were only associated with waist and diastolic BP (both P<0.05). After adjusting for age, centre, season and lifestyle factors the odds for MetS decreased across increasing 25(OH)D quintiles (odds ratios 0.48 (95% confidence intervals 0.36-0.64) highest versus lowest quintile; P(trend)<0.001). This relationship was unchanged after adjustment for PTH, but was attenuated after additional adjustment for homoeostasis model assessment of insulin resistance (0.60 (0.47-0.78); P(trend)<0.001). There was no association between PTH and MetS. Our results demonstrate an inverse relationship between 25(OH)D levels and MetS, which is independent of several confounders and PTH. The relationship is partly explained by insulin resistance. The clinical significance of these observations warrants further study.