Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulations of amyloid -β (Aβ) peptides. Multidrog resistance 1 (MDR1)/ABCB1 gene encodes P-glycoprotein (P-gp), which play a role in Aβ elimination from the brain. Cerebral amyloid deposition in patients with AD was inversely correlated with brain capillary P-gp expression. Our study was undertaken to confirm the hypothesis that the C3435T (rs1045642) and the G2677T/A (rs2032582) polymorphisms of the MDR1 gene represent risk factors for AD. A total of 242 patients with AD and 226 elderly, cognitively intact, healthy control subjects were recruited. the clinical diagnosis of AD fulfilled the criteria for NINCDS-ADRDA. the genetic analyses were performed by PCR-RFLP. the C/C and C/T genotypes of the C3435T polymorphism was significantly over-represented in AD as compared to HC group (p < 0.001). the allele distribution of the C3435T polymorphism also showed statistically significant difference between cases and controls with higher C allele frequency in the AD group (p < 0.001). the C allele carriers had a significantly increased risk for AD (OR = 3.53, 95%CI:2.19–5.68, p = 0.005) considering the T/T genotype as reference category (OR = 1). the genotype and allele frequencies of the G2677T/A polymorphism did not differ significantly between the AD and HC groups (p = 0.801 for genotypes, and p = 0.754 for alleles). Our findings indicate that the C allele of the C3435T polymorphism may confer risk for developing AD. We failed to detect an association between G2677T/A polymorphism and AD. This work was supported by grants from the Hungarian Ministry of Health 052-07/2009 and TÁMOP-4.2.1/B-09/1/KONV-2010-0005.