Background: The frequent association of nonalcoholic fatty liver disease with components of the metabolic syndrome such as obesity, hyperglycemia, dyslipidemia, and hypertension is well known. However, no prospective study has examined the role of the metabolic syndrome in the development of this disease. Objective: To characterize the longitudinal relationship between the metabolic syndrome and nonalcoholic fatty liver disease. Design: A prospective observational study. Setting: A medical health checkup program in a general hospital. Participants: 4401 apparently healthy Japanese men and women, 21 to 80 years of age, with a mean body mass index (BMI) of 22.6 kg/m2 (SD, 3.0). Measurements: Alcohol intake was assessed by using a questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome. Results: At baseline, 812 of 4401 (18%) participants had non-alcoholic fatty liver disease. During the mean follow-up period of 414 days (SD, 128), the authors observed 308 new cases (10%) of nonalcoholic fatty liver disease among 3147 participants who were disease-free at baseline and who completed a second examination. Regression of nonalcoholic fatty liver disease was found in 113 (16%) of 704 participants who had the disease at baseline and who completed a second examination. Men and women who met the criteria for the metabolic syndrome at baseline were more likely to develop the disease during follow-up (adjusted odds ratio, 4.00 [95%CI, 2.63 to 6.08] and 11.20 [CI, 4.85 to 25.87], respectively). Nonalcoholic fatty liver disease was less likely to regress in those participants with the metabolic syndrome at baseline. Limitations: Ultrasonography may lead to an incorrect diagnosis of nonalcoholic fatty liver disease in 10%to 30%of cases and cannot distinguish steatohepatitis from simple steatosis. Selfreported alcohol intake may cause bias. Because all of the participants were Japanese, generalizability to non-Japanese populations is uncertain. Conclusions: The metabolic syndrome is a strong predictor of nonalcoholic fatty liver disease. Background: The frequent association of nonalcoholic fatty liver disease with components of the metabolic syndrome such as obesity, hyperglycemia, dyslipidemia, and hypertension is well known. However, no prospective study has examined the role of the metabolic syndrome in the development of this disease. Objective: To characterize the longitudinal relationship between the metabolic syndrome and nonalcoholic fatty liver disease. Design: A prospective observational study. Setting: A medical health checkup program in a general hospital. Participants: 4401 apparently healthy Japanese men and women, 21 to 80 years of age, with a mean body mass index (BMI) of 22.6 kg / m2 (SD, 3.0). Measurements: Alcohol intake was assessed by using a questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome. Results: At bas During the mean follow-up period of 414 days (SD, 128), the authors observed 308 new cases (10%) of nonalcoholic fatty liver disease among 3147 participants who were disease-free at baseline and who completed a second examination. Regression of nonalcoholic fatty liver disease was found in 113 (16%) of 704 participants who had the disease at baseline and who completed a second examination. Men and women who met the criteria for the metabolic syndrome at baseline were more likely to develop the disease during follow-up (adjusted odds ratio, 4.00 [95% CI, 2.63 to 6.08] and 11.20 [CI, 4.85 to 25.87], respectively) liver disease was less likely to regress in those participants with the metabolic syndrome at baseline. Limitations: Ultrasonography may lead to an incorrect diagnosis of nonalcoholic fatty liver disease in 10% to 30% of cases and can not distinguish steatohepatitis from simple steatosisBecause all of the participants were Japanese, generalizability to non-Japanese populations is uncertain. Conclusions: The metabolic syndrome is a strong predictor of nonalcoholic fatty liver disease.