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Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited. Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH). Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup. Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m2 (n = 125) was 79.6 (78.0; 81.2) ml/min/1.73m2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m2 at 12 months after switch. In the patient-matched subgroup (n = 175), median annual eGFR-EPI declined −4.24 ml/min/1.73m2 while on F/TDF and increased +0.93 ml/min/1.73m2 after switch to F/TAF (P < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m2, median annual eGFR-EPI increased +4.19 mL/min/1.73m2 after switch (P < 0.0001). Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m2. eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting.