<i>Background:</i> Genotypes of the solute carrier family 6 (neurotransmitter transporter, serotonin) member 4 (SLC6A4) have been variously associated with depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding their association with severe dementia, in particular with vascular dementia (VaD). <i>Aims:</i> To evaluate the possible involvement of different SLC6A4 genotypes/haplotypes in VaD. <i>Methods:</i> The analysis of the 3 markers rs3813034, rs140701 and rs4795541 spanning the SLC6A4 locus was made in 541 consecutive patients clinically diagnosed as having VaD (n = 372) or no cognitive impairment (n = 169) attending a geriatric ward. A community-dwelling sample of 353 healthy subjects, as a reference for the genetic frequencies in the recruitment area, was also included in the study. All patients and subjects were free from any symptoms of depression, obsessive-compulsive disorder and anxiety. A complete neuroimaging documentation was available for all patients. <i>Results:</i> No important differences were observed in genotype distribution across the study groups. Similarly, no important differences were observed in haplotype distribution when a 3-point analysis was made. <i>Conclusion:</i> Our findings suggest that polymorphism C in the promoter region of the SLC6A4 gene plays a minor role, if any, in the pathogenesis of VaD.