Objective: To examine the effect of variants in genes encoding molecules that are implicated in leukocyte trafficking into the CNS on the development of MS.Methods: A total of 389 Greek MS cases and 336 controls were recruited by 3 MS centers in Cyprus and Greece. In total, 147 tagging single nucleotide polymorphisms across 9 genes encoding for P-selectin (), integrins (, , and ), adhesion molecules (, , and , fibronectin 1 (), and osteopontin () were genotyped. The clinical end point of the study was diagnosis of MS according to the 2005 revised McDonald criteria. Permutation analysis was used for adjusting for multiple comparisons.Results: Overall, 21 variants across , , , , , , , and genes were each associated with MS ( < 0.05). The most significant were rs3917779 and rs2076074 (), rs6721763 (), and rs1250258 (), all with a permutation value of less than 1e-004.Conclusions: The current study provides preliminary evidence that variants across genes encoding adhesion molecules, responsible for lymphocyte adhesion and trafficking within the CNS, are implicated in the risk of developing MS.