Familial hypercholesterolemia (FH) subjects have high low-density lipoprotein cholesterol (LDL-C) and may be at high risk of erectile dysfunction and atherosclerotic cardiovascular diseases. We evaluated the effect of PCSK9-i on sexual function evaluated by the Male Sexual Health Questionnaire (MSHQ) and the International Index of Erectile Function (IIEF-5) questionnaire and on pulse wave velocity (PWV) in FH male subjects. In this prospective observational study, we evaluated 30 FH male patients on high-intensity statins plus ezetimibe and with an LDL-C off-target. All patients added PCSK9-i treatment and obtained clinical assessment at baseline and after six months of PCSK9-i. As expected, LDL-C significantly decreased after adding-on PCSK9-i (−48.73%, p < 0.001). MSHQ and PWV significantly improved after adding-on PCSK9-i (for MSHQ 93.63 ± 6.28 vs. 105.41 ± 5.86, p < 0.05; for PWV 9.86 ± 1.51 vs. 7.7 ± 1.42, p < 0.05); no significant change of IIEF-5 was found. Finally, a simple regression showed that ∆ MSHQ was significantly associated with ∆ LDL-C and ∆ PWV (p value for both <0.05). In conclusion, PCSK9-i therapy significantly improves lipid profile, PWV, and sexual function in FH male patients; our results support the favorable function of PCSK9-i on these parameters.