The association between selected mannose-binding lectin (MBL) genotype polymorphisms and Wuchereria bancrofti infection status was assessed among individuals whose infection status had been monitored for three decades. Blood samples were collected in 2006 and examined for polymorphisms in the mbl-2 gene and for W. bancrofti-specific circulating filarial antigen (CFA) status. Logistic regression analysis showed a significant association between MBL genotype and CFA status, with low-expression MBL genotype individuals being almost three times more likely to be CFA positive than high-expression MBL genotype individuals (odds ratio [OR] = 2.90). When individuals' filarial infection (microfilaria) status in 1975 was included in the analyses, the gain of new infections between the two examination points was almost 10 times higher among individuals with low than among those with high MBL expression genotype (OR = 9.51). The susceptibility to W. bancrofti infection thus appears to be significantly affected by the MBL expression genotype of the host.