The Aim of this study is to assess the cardiovascular safety of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF). We analyzed data from 37 virologically suppressed people living with HIV starting DOR/3TC/TDF, collecting viro-immunological and metabolic parameters as well as the 10-year risk of cardiovascular disease (10Y-CD) using both the Framingham risk score and D:A:D score.After 48 weeks, we observed a significant reduction in 10Y-CD both via the Framingham score (-0.7, p = .021) and the D:A:D score (-0.41, p = .012). After 96 weeks, we registered a significant reduction in 10Y-CD calculated via the D:A:D score (-0.98, p = .009). Regarding serum lipid markers, after 48 weeks we observed a significant reduction in total cholesterol (-17 mg/dL, p < .001), triglycerides (-21 mg/dL, p = .015), and LDL cholesterol (-8 mg/dL, p = .022). After 96 weeks, we registered a significant reduction in total cholesterol (-19 mg/dL, p < .001). DOR/3TC/TDF has shown a favorable metabolic profile, with a significant reduction in 10Y-CD, independently from the use of lipid-lowering drugs.