Some papers have suggested that alkaline phosphatase (ALP) level is a predictor of the metabolic syndrome (MetS) in the general population. However, the association is still controversial, and the mechanisms underlying an association between ALP level and the MetS have not been elucidated. We analyzed the association between serum ALP level and the development of the MetS over a 4-year period. A total of 14,224 subjects who visited the Health Promotion Center for a medical examination in 2005 were followed up after 4 years. Serum ALP level correlated positively with body fat mass and visceral fat mass. The adjusted geometric mean ALP levels were higher in subjects with elevated C-reactive protein level or greater fat mass (P < 0.001). None of the subjects had the MetS at baseline, but 1,179 exhibited the MetS at the 4-year follow-up. After multiple adjustments, the odds ratio (OR) was substantially higher for development of the MetS (OR 1.56, 95% confidence intervals, 1.21-2.01) in subjects in the highest ALP quintile compared with those in the lowest quintile. After adjusting for various covariates, we found significant associations between the quintile of serum ALP level and abdominal obesity, low high-density lipoprotein cholesterol level, and high triglyceride level. Higher serum ALP level was a significant predictor of the MetS in middle-aged Koreans. Serum ALP level correlated positively with body fat mass and independently with a more atherogenic lipid profile in the general population in Korea.