Aim: The aim of this study was to analyze the association between longitudinal physical activity patterns (persistently inactive, became active, became inactive, and persistently active) and the incidence of Metabolic Syndrome (MS) among adults. Methods: Our cohort included 5766 adults (18-59y) undergoing repeated routine health screening examinations, with a mean follow-up period of three years. Only subjects without MS at baseline were included in the study. MS was defined according to the ATP III definition, including assessments of fasting blood samples for the collection of HDL-C, triglycerides and glucose, blood pressure, and waist circumference. Physical activity was estimated using the international physical activity questionnaire and four patterns were created (persistently active, became active, became inactive, and persistently inactive). Information on tobacco smoking and alcohol consumption (through structured validated questionnaires), age, interval between baseline and follow-up, anti-hypertensive drugs, statin, anti-diabetic drugs were used as covariates. Logistic regression was conducted. Results: The mean age of participants at baseline was 41.6 ± 7.9 years. We identified 1701 subjects who were active at both moments, 1246 who became active, 709 who became inactive, and 2210 who were inactive at both moments. Persistently inactive subjects presented a higher incidence of MS [10.4% (95%CI = 9.2–11.8%)]. In the adjusted logistic regression analyses, subjects that became active [OR = 0.55(95%CI = 0.40–0.74)] and persistently active [OR = 0.35(95%CI = 0.26–0.46)] were less likely to develop MS when compared with persistently inactive subjects. Conclusion: Persistently active subjects demonstrated the lowest likelihood of developing MS, while subjects who became active presented an attenuated risk.