Several studies have reported on metabolic syndrome (MetS) based on cross-sectional designs, which cannot show a long-term result. Information is lacking on MetS and related factors based on a longitudinal cohort. This study aimed to examine the relationship between MetS and related factors for a total of six years among hospital employees. A population-based study was conducted, including 746 staff. A total of 680 staff without MetS in 2012 were enrolled in the analysis for repeated measurement of six years of the longitudinal cohort. Data were retrieved from the hospital’s Health Management Information System. Analyses were performed using Student’s t-test, chi-square test, logistic regression, and generalised estimating equations. Statistical significance was defined as p < 0.05. Hospital employees aged between 31 and 40 (odds ratio (OR) = 4.596, p = 0.009), aged between 41 and 50 (OR = 7.866, p = 0.001), aged greater than 50 (OR = 10.312, p < 0.001), with a body mass index (BMI) of 25.0~29.9 kg/m2 (OR = 3.934, p < 0.001), a BMI ≥ 30 kg/m2 (OR = 13.197, p < 0.001), higher level of white blood counts (β = 0.177, p = 0.001), alanine aminotransferase (β = 0.013, p = 0.002), and uric acid (β = 0.223, p = 0.005) were at risk of being diagnosed with MetS. The identification of at-risk hospital employees and disease management programs addressing MetS-related factors are of great importance in hospital-based interventions.