The pathogenesis of delayed ejaculation (DE) is rather unknown, though the contribution of various psychological, marital, hormonal, and neurological factors has been advocated. In this study we systematically investigated the relative relevance of the aforementioned factors in 1,632 men who were seeking medical help for sexual dysfunction. The severity of DE was classified according to Kaplan criteria. Mild and moderate forms of DE (MMDE) recognized different risk factors than the most severe ones (anejaculation or severe DE [ASDE]). ASDE was essentially coupled with the presence of neurological diseases or with the use of serotoninergic drugs. Serotoninergic drugs also significantly increase (by at least 10-fold) the risk for MMDE, which, however, was also coupled with other relational factors (eg, partner's impaired climax, patient's hypoactive sexual desire [HSD]) or intrapsychic factors (eg, stress at work). At multiple regression analysis, some organic pathological conditions (such as psychiatric disorders and hypogonadism) were also associated with MMDE. In particular, hypogonadism retained significance for DE even after adjustment for HSD (adjusted odds ratio = 2.08 [1.11-3.89]; P < .05), suggesting other effects of testosterone deficiency on the ejaculatory reflex besides reduced libido. In conclusion, the present study demonstrates that multiple psychobiological determinants are associated with DE, a still obscure condition that substantially impairs psychosexual equilibrium of the couple.