We evaluated the effect of a chronic treatment with Tadalafil on progenitor cells (PCs) number and endothelial function in patients with erectile dysfunction (ED) with or without cardiovascular risk factors. Twenty-six subjects with ED and 23 aged matched controls were studied. All subjects underwent blood tests, International Index of Erectile Function (IIEF-5), Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), brachial artery flow-mediated dilation (FMD) and PCs count. International index of erectile function, FMD and PC count were re-evaluated in all subjects at the end of Tadalafil and placebo treatment. With respect to controls patients had lower basal FMD (P < 0.05) and basal PCs (P < 0.05). Treatment with Tadalafil determined a significant increase in PCs (P < 0.001) and FMD (P < 0.001) with respect to basal level. Positive correlation was found between basal FMD and PCs (P < 0.05) and between basal FMD and PCs increase after Tadalafil treatment (P < 0.05). Tadalafil promotes a mobilization of PCs and improves endothelial function in ED patients.