The objective of the study was to determine the association between intron 4 variable number of tandem repeats (VNTR), E298A and IVF 23+10 G/T polymorphisms of ec-NOS gene and sildenafil responsiveness in patients with erectile dysfunction (ED). Ninety-six patients who were evaluated for ED between November 2003 and June 2004 and 167 healthy individuals representing the normal population as controls were included in the present study. The patients were evaluated by medical history, five-item version of International Index of Erectile Function, serum glucose, testosterone levels and lipid profiles. Sixty-seven patients received four consecutive doses of sildenafil from 25 to 100 mg according to the response. The ec-NOS gene intron 4 VNTR, E298A and IVF 23+10 G/T polymorphisms were evaluated in the isolated DNA blood samples obtained from the patient group with ED (n=96), from the group received sildenafil (n=67) and from the healthy group (n=167). Genotype distributions of ec-NOS gene intron 4, E298A and IVF 23+10 G/T polymorphisms in the patient group were similar to those in the healthy group. The frequency of the ec-NOS gene intron 4 genotype were found as bb=41.7%, ab=50% and aa=8.3% in the sildenafil responders and bb=93.5% and ba=6.5% in the sildenafil non-responders. This finding was statistically significant. Statistical analysis of ec-NOS gene E298A and IVF 23+10 G/T polymorphisms did not reveal any significant difference between sildenafil responders and non-responders. These findings may indicate that 'a' allele of ec-NOS gene intron 4 VNTR polymorphism associates with a better sildenafil response.