The aim of the study was to establish whether metabolic syndrome predicts the incidence of prostate cancer. The hypothesis was tested using the 27-year follow-up of the prospective cohort of 16,209 men aged 40–49 years who participated in the Oslo Study in 1972–1973. Men with established diabetes and men with cancer diagnosed before screening were excluded, leaving 15,933 for analyses. Metabolic syndrome is here composed of body mass index, nonfasting glucose, triglycerides, and blood pressure or drug-treated hypertension. Two analytical approaches were compared, namely, predefined (adjusted from National Cholesterol Education Program) and quartile values of risk factors. Age, body mass index, and sedentary versus intermediate physical activity at work were significant predictors in univariate proportional hazards regression analyses. Combinations of any two (relative risk = 1.23; p = 0.04) or any three (relative risk = 1.56; p = 0.00) factors of the metabolic syndrome using quartile values of risk factors were predictive of prostate cancer. The number of cases for four factors was too small for analyses. Predefined values of the risk factors were not found to be predictive. In conclusion, metabolic syndrome was found to predict prostate cancer during 27 years of follow-up, indicating an association between insulin resistance and the incidence of prostate cancer.