AIM To compare the effectiveness of the phosphodiesterase type 5 inhibitor (PDE-5i) tadalafil alone and in combination with a biologically active dietary supplement (BADS) NeyroDoz, containing the precursors of serotonin in patients with erectile dysfunction (ED) associated with secondary premature ejaculation (SPE). MATERIAL AND METHODS 105 patients (mean age 36.2+/-9.1 years) with concomitant ED and SPE were included in a prospective study and divided into 2 groups. The patients of group 1 (n=47) received PDE-5i 5 mg daily for 1 month. In patients of group 2 (n=58) PDE-5i was co-administered with BADS 2 capsules twice daily. Treatment efficacy was evaluated using "Criteria for premature ejaculation" (CriPE) and IIEF-5 questionnaires at baseline and on completion of the treatment course. Besides, a polymorphism in the serotonin transporter gene (5-HTTLPR) was tested. RESULTS The treatment was effective in 35 (74.5%) and 48 (82.7%) patients of group 1 and 2, respectively (p<0.0001) with similar statistically significant (p<0.001) improvement in erectile function. According to CriPE scores, 6.4, 8.5, 23.4, 10.6 and 12.8% patients of group 1 and 10.3, 1.7, 40.0, 25.9, 10.3 and 31.0% patients of group 2 with LaLa, LaLg, LgLg, Sla, SLg, SS genotypes were rendered free of SPE, respectively. CONCLUSION Treating ED-associated SPE with the combination of serotonin precursors and tadalafil can better improve ejaculatory function recovery compared with PDE-5i monotherapy.