Aims Cross-sectional evidence indicates that abdominal adiposity, hypertension, dyslipidaemia and glycaemia are associated with reduced metabolic clearance rate of insulin (MCRI). Little is known about the progression of MCRI and whether components of metabolic syndrome are associated with the change in MCRI. In this study, we examined the association between components of metabolic syndrome and the 5-year change of MCRI. Methods At baseline and 5-year follow-up, we measured fasting plasma triglycerides (TG), high-density lipoprotein (HDL) cholesterol, blood pressure (BP), waist circumference (WC) and fasting blood glucose (FBG) in 784 non-diabetic participants in the Insulin Resistance Atherosclerosis Study. MCRI, insulin sensitivity (SI) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Results We observed a 29% decline of MCRI at follow-up. TG, systolic BP and WC at baseline were inversely associated with a decline of MCRI regression models adjusted for age, sex, ethnicity, smoking, alcohol consumption, energy expenditure, family history of diabetes, BMI, SI and AIR [β = −0.057 (95% confidence interval, CI: −0.11, −0.0084) for TG, β = −0.0019 (95% CI: −0.0035, −0.00023) for systolic BP and β  = −0.0084 (95% CI: −0.013, −0.0039) for WC; all p < 0.05]. Higher HDL cholesterol at baseline was associated with an increase in MCRI [multivariable-adjusted β = 0.0029 (95% CI: 0.0010, 0.0048), p = 0.002]. FBG at baseline was not associated with MCRI at follow-up [multivariable-adjusted β = 0.0014 (95% CI: −0.0026, 0.0029)]. Conclusions MCRI declined progressively over 5 years in a non-diabetic cohort. Components of metabolic syndrome at baseline were associated with a significant change in MCRI.