Mannose-binding lectin (MBL) may be involved in the biologic cascade of events initiated by wear debris and bacterial infection around loosened total hip arthroplasties (THAs). Individual responses to such stimuli may be dictated by genetic variation caused by single nucleotide polymorphisms (SNPs). We performed a case-control study on 4 MBL SNPs using case patients (n = 91) with aseptic loosening or deep infection (n = 71). Control subjects (n = 150) had clinically and radiologically well-fixed THAs for more than 10 years. Frequency of the C allele (P = .001) and that of the genotype C/C (P = .004) for the -550 SNP were associated with aseptic failure. The codon 54 SNP G allele (P = .012) and G/G genotype (P = .027) frequencies were associated with aseptic failure as well. In the septic group, the frequency of the C allele (P = .01) and that of the genotype C/C (P = .05) for the -550 SNP were significant. Failure of THAs may be under genetic influence to candidate susceptibility genes such as MBL.