The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by the gene PON1 (chromosome 7q21.3) plays a role as an antioxidant molecule through several mechanisms. Because oxidative stress has been implicated in the pathogenesis of migraine, we have investigated the possible association between the nonsynonymous polymorphisms 55LM and 192QR in the PON1 and the risk for migraine. We studied the frequency of the PON1 genotypes and allelic variants in 197 patients with migraine and 220 healthy controls using a TaqMan single nucleotide polymorphism analysis. The frequencies of the PON1 genotypes and PON1 allelic variants did not differ significantly between patients with migraine and controls, and were unrelated with gender, family history of migraine, and presence or absence of aura. The frequencies of the genotype PON1 192QQ and the allelic variant PON1 192Q were significantly higher in patients with earlier onset of migraine. The results of the present study suggest that PON1 polymorphisms are not related with the risk for migraine in Caucasian Spanish people, although PON1 192Q/Q genotype and PON1 192Q allelic variant should be related with an earlier onset of migraine.