Abstract Background and Aims Renal hyperfiltration (RHF) and metabolic syndrome (MetS) increase the risk of cardiovascular disease, end stage kidney disease (ESKD), and all-cause mortality. While RHF is strongly related to the metabolic risk, it is little known how the combined association of these two factors affects the risk of MetS-related complication, cardiovascular disease, and all-cause mortality. Method We reviewed the National Health Insurance Service database of Korea for people who received national health screenings between 2009 and 2011. RHF was defined as estimated glomerular filtration rate (eGFR) > 95th percentile after stratification for age, sex, height and weight, and normal renal filtration defined as eGFR 25-75th percentile. MetS was considered as the presence of three or more of the metabolic risks. Individuals were compared based on the presence of RHF and MetS. Age, sex, and Charlson comorbidity index matching were performed to reduce the selection bias in the study population. Finally, a total of 276,952 patients were matched, with 69,238 patients in each group, in a 1:1:1:1 ratio based on both their metabolic status and the presence of RHF. Results In multivariate Cox analysis, in comparison to normal renal filtration without MetS, RHF without MetS does not increase the risk of progression to ESKD. RHF patients increased the risk of progression to ESKD (aHR 2.75, 95% CI 1.38-5.50) only when combined with MetS. Moreover, irrespective of metabolic status, the risk of cardiovascular events (without MetS: aHR 1.08, 95% CI 1.00-1.17), (with MetS: aHR, 1.49; 95% CI, 1.38-1.60) and all-cause mortality (without MetS: aHR 1.29, 95% CI 1.20-1.40), (with MetS: aHR, 1.49; 95% CI, 1.37-1.62) increases significant in RHF patients. Notably, RHF synergistically increases the risk of cardiovascular events when accompanied with MetS (p for interaction = 0.041). However, RHF increases the risk of all-cause mortality more significantly without MetS than with MetS (p for interaction = 0.005). Conclusion The clinical implication of RHF is dependent on MetS status, and a significant interaction between the two factors is observed. To establish a treatment strategy for patients with RHF, MetS status must be considered.