Objective To explore the impact of long-term administration of different nucleos(t)ide analogues on estimated glomerular filtration rate (eGFR) in post-liver transplantation patients with chronic hepatitis B virus (HBV) infection. Methods In this retrospective clinical cohort study, we included 177 post-liver transplantation patients treated with entecavir (ETV; ETV group), telbivudine (LDT; LDT group), lamivudine (LAM; LAM group) or adefovir dipivoxil (ADV; ADV group) between Aug. 2008 and Oct. 2014 in our hospital, and clinical data of all patients were analyzed. The eGFR levels in post-operation of 3 (baseline), 9, 15, 21 and 27 months were analyzed by modification of diet in renal disease (MDRD) formula and chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Logistic regression method was used to analyze risk factors for ≥ 20% mean change of baseline eGFR level at 27 months after operation. Results Sixty-six of 177 patients received treatment with ETV, 21 with LDT, 61 with LAM and 29 with ADV. Compared with baseline, the eGFR levels of the patients in LAM group and ADV group were significantly decreased at 9 months after liver transplantation (P<0.05), and there was a decreasing tendency during the 27-month follow-up (P<0.001). However, the eGFR level of the patients in LDT group showed a significant increase at 9 months after post-operation (P<0.05), and there was an increasing tencdency during the 27-month follow-up (P<0.001). There was no significant change in eGFR level during the follow-up period in ETV group. Multivariate logistic regression analysis showed that LAM or ADV treatment were independent risk factors for ≥ 20% decrease in the eGFR level at 27 months after operation compared with baseline (P<0.01), and baseline blood urea nitrogen level and LDT treatment were independent predictive factors for ≥ 20% increase in the eGFR level (P<0.01). Conclusion In post-liver transplantation patients, long-course treatment with LAM or ADV may be a potential cause of nephrotoxicity, while LDT treatment can increase the patient's eGFR level, and ETV has no significant influence on the eGFR.