Despite a close association between adiponectin and both hypertension and type 2 diabetes, the relationship between adiponectin and metabolic syndrome has not yet been well-investigated. To examine and evaluate the association between serum adiponectin levels and metabolic syndrome based on Japanese diagnostic criteria, we analyzed adiponectin and anthropometric parameters in 869 male employees aged 40-59 who belonged to a health insurance society in Fukuoka Prefecture and who underwent annual health check-ups from August 2006 to July 2007. Two hundred and thirty-two of the 869 subjects (26.7%) were diagnosed with metabolic syndrome. The serum adiponectin levels were significantly higher in the non-metabolic syndrome group. In a multiple logistic regression analysis, the subjects in the top quartile of serum adiponectin (adjusted odds ratio: 0.36; 95% confidence interval: 0.21-0.63) and the second (adjusted odds ratio: 0.51; 95% confidence interval: 0.31-0.84) quartile had a significantly decreased risk for metabolic syndrome in comparison to the bottom quartile. The dose-response relationship between serum adiponectin levels and metabolic syndrome was significant (p for trend < 0.0001) after adjusting for age, body mass index, smoking status, and drinking status. The current findings suggest that hypoadiponectinemia is inversely correlated with the risk of metabolic syndrome in middle-aged Japanese male workers.