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In patients with chronic hepatitis B (CHB), long‐term effects of tenofovir disoproxil fumarate (TDF) on renal function have been controversial. This study aimed to analyse the real‐world long‐term effects of TDF on renal function in Korean patients with CHB. We analysed a cohort of 640 treatment‐naïve patients with CHB who were treated with TDF between May 2012 and December 2015 at Severance Hospital, Seoul, Republic of Korea. The mean age was 48.3 years old, and 59.5% were male. The proportions of hypertension and diabetes mellitus (DM) were 11.6% and 14.2%, respectively, and that of liver cirrhosis was 20.8%. During the 5‐year follow‐up, using a linear mixed model, serum creatinine increased from 0.77 ± 0.01 mg/dL to 0.85 ± 0.02 mg/dL (P <.001), and eGFR decreased from 102.6 ± 0.6 mL/min/1.73 m2 to 93.4 ± 1.4 mL/min/1.73 m2 (P <.001). In subgroup analysis, eGFR was statistically more decreased in patients with age > 60 than ≦60 years old (P =.027), and in patients with diuretic use than without diuretic use (P =.008). In multivariate analysis, the independent risk factors for eGFR decrease > 20% were baseline eGFR < 60mL/min/1.73 m2 (P =.034) and the use of diuretics (P <.001). CHB patients on TDF experienced greater reduction in renal function with age > 60 and with diuretic use compared to those without these characteristics. Baseline eGFR < 60 mL/min/1.73 m2 and use of diuretics were independent risk factors of eGFR decline of more than 20% on TDF therapy. [ABSTRACT FROM AUTHOR]