Otosclerosis (OTSC) is one of the most common causes of hearing loss in white adults. The COL1A1 and COL1A2 genes coding for type-I collagen have been proposed as candidate genes in the development of OTSC. The COL1A1 gene was recently reported to be associated with the condition on the basis of a population-based case-control study. We report here an independent study of association between COL1A1 and COL1A2 gene polymorphisms and OTSC, in a case-control sample from a population of Caucasian individuals living in Northwest Spain. Specifically, we studied two COL1A1 polymorphisms previously reported to be associated with OTSC, and six COL1A2 polymorphisms. We performed diverse association analyses based on alleles, genotypes, and two-locus haplotypes. We found no evidence supporting the putative link of COL1A1 and COL1A2 genes with OTSC.