OBJECTIVE To evaluate the possible improvement of sexual activity following a non on-demand administration of a long half-life selective inhibitor of phosphodiesterase type 5 (PDE-5) in elderly patients without major cardiovascular risk factors. METHODS Sixty subjects with erectile dysfunction (ED) aged 60-70 years and 30 control patients aged 18-40 years, affected by psychogenic ED, were studied. All underwent routine and hormonal blood tests, Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), ultrasonographyc evaluation of common carotid artery intima-media thickness (IMT) and penile colour Doppler ultrasonography (P-CDU). All patients underwent therapy with tadalafil 20 mg in alternative days, non on-demand, at 5.00 p.m., for three consecutive months. IIEF-5, NPTRM test and P-CDU were re-evaluated one month after the end of the therapy. RESULTS Among elderly subjects 20 (33%) had normal carotid IMT (< 0.9 mm), 15 (25%) minimal increase of carotid thickness (IMT = 0.9-1.2 mm) and 25 (42%) one or more carotid plaques (IMT > 1.3 mm). NPTRM and P-CDU parameters were inversely related to different degrees of carotid wall alteration and showed a significant improvement respect to pre-treatment only in patients without atherosclerotic plaques. Also IIEF-5 showed significant improvements only in patients without atherosclerotic plaques. CONCLUSIONS In elderly subjects with slight or no signs of vascular disease at the carotid level, chronic and non on-demand treatment with tadalafil can induce spontaneous resumption of erections, probably through the improvement of endothelial function, but direct evidences to confirm this hypothesis are required.