Antiretroviral treatment based on tenofovir alafenamide fumarate (TAF) is increasingly recommended, as it maintains the viral suppression and improves renal function and bone density in comparison with tenofovir disoproxil fumarate (TDF). We carried out a retrospective cohort study including experienced patients who switched treatment from TDF to TAF. Serum lipids and glucose, renal function, body mass index (BMI), and cardiovascular risk were evaluated before and 3 and 6 months after the initiation of TAF-based treatment. We identified 85 patients on TAF-based treatment. The majority were men (82.9%), smokers (70%), and older than 40 years. Significant increases in lipids and BMI were noted, but cardiovascular risk remained <7.5%. Renal function remained normal with a notable improvement among patients with renal impairment. These results suggest that TAF has no significant effect on glucose and does not meaningfully increase cardiovascular risk, despite an elevation in serum lipids. It also exhibits renal safety. However, the increase of BMI was significant. Further studies are needed to confirm these findings in larger patient series and over longer follow-up periods.