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Background: The association between orthostatic hypotension (OH) and long-term changes in kidney function in the general population is not yet well known. Methods: We performed a population-based cohort study based on data from the Korean Genome and Epidemiology Study (KoGES). The primary exposure was the presence of classic OH, defined as a postural drop in blood pressure (systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg) at 2 min of standing after 5 min of supine rest. The primary outcome was a 12-year change in kidney function, assessed by subtracting the baseline estimated glomerular filtration rate (eGFR) from the eGFR at 12 years of follow-up. Results: Our study included 5,905 participants (median [interquartile range] age, 49 [44–58] years; 46% males) who met inclusion and exclusion criteria. Classic OH was detected in 268 (4.5%) of the total participants. In the regression analyses, participants with classic OH had a greater decline in eGFR over 12 years compared with those without classic OH; the fully adjusted beta coefficient and 95% confidence intervals (95% CIs) were −1.74 (−3.07, −0.40). Furthermore, classic OH was associated with 27% greater risk of a 30% decline in kidney function compared with those without classic OH; fully adjusted hazard ratio and 95% CIs were 1.27 (1.07, 1.49). Conclusions: Classic OH can negatively affect long-term kidney function in the general population.