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Two elvitegravir/cobicistat-based therapies combined with emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) or emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) are currently available for HIV patients. This study evaluated the modifications in the lipid profile of patients who received these treatments in the last three years at our institution. A retrospective observational study in HIV-infected patients who received EVG/c/FTC/TDF or EVG/c/FTC/ TAF from January 2015 to January 2018 at a reference hospital in northwestern Spain was carried out. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software. A total of 384 EVG/c-based therapies were initiated during the study period, 151 EVG/c/ FTC/TDF and 233 EVG/c/FTC/TAF. A significantly negative influence in all the lipid profile parameters in experienced patients and total cholesterol (TC), and LDL-C in naïve patients were observed after 48 weeks of treatment with EVG/c/ FTC/TAF, while these parameters remained stable in the EVG/c/FTC/TDF group.During follow-up, a greater proportion of patients had lipid levels above the normal range (63.1% TC, 56.2% LDL-C) and new lipid-modifying drugs were prescribed (11.9%) in the EVG/c/FTC/TAF group. The number of cardiovascular risk factors (OR 1.66 [95% CI 1.01-2.72]; P = 0.043) was recognised as an independent predictor of lipid-lowering prescription for patients treated with both EVG/c/FTC/TDF and EVG/c/FTC/TAF. For patients treated with EVG/c/FTC/ TAF, the mean total cholesterol to HDL ratio in the first 48 weeks of the study treatment was associated with a higher likelihood of lipid-lowering prescription in multivariate analysis (OR 1.6 [95% CI 1.12-2.52]; P = 0.011). Significant changes in lipid profile have been observed in patients who have received EVG/ c/FTC/TAF. It was necessary to prescribe almost twice the number of lipid-lowering drugs to patients who received EVG/c/FTC/TAF (11.9%) vs EVG/c/FTC/ TDF (4.7%).