Objective: Growing evidence suggests that increased adiponectin levels may play a protective role in the development of metabolic syndrome (MetS). We investigated whether increased serum adiponectin is a negative predictor of incident MetS in a population-based longitudinal study in Korea. Methods: We analyzed data from 2,675 adults (1,250 men and 1,425 women) without MetS, aged 40 to 70 years assessed in the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in Korean General Population (KoGES-ARIRANG). MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III report and the World Health Organization Asian Pacific Guideline. Results: During an average of 2.5 years of follow-up, MetS was developed in 413 men and 425 women. The median adiponectin levels at baseline in subjects who developed MetS were significantly lower than those who did not in men and women. The highest quartile of adiponectin level in men (≥10.21 μg/mL) were associated with significantly decreased risk of new-onset MetS (HR, 0.30; 95% CI, 0.21-0.43) as well as all components of MetS after adjustment for age, smoking, alcohol intake, exercise and HOMA-IR. The highest quartile of adiponectin level in women (≥14.40 μg/mL) were also associated with decreased risk of new-onset MetS (HR, 0.27; 95% CI, 0.19-0.38) as well as all components of MetS. Conclusion: Our findings suggest that increased serum adiponectin could be a negative predictor of incident MetS and its components.