The fast development in high-throughput single nucleotide polymorphism (SNP) genotyping technology provides unprecedented power for genome-wide SNP association studies. However, inaccurate genotyping can lead false association between markers and phenotype. We introduce a new SNP genotyping scheme, SNiPer 500K, Affymetrix 500K GeneChip. SNiPer 500K designs a parametric classifier for each SNP, by using expectation-maximization algorithm to estimate the parameters. A quality index provided by SNiPer 500K shows that it can reliably genotype about 65% of all SNPs, with superior call rate, better Hardy-Weinberg Equilibrium and reproducibility. SNiPer 500K provides a good balance between coverage and accuracy for high-throughput SNP genotyping and would prove to be an invaluable tool genome-wide association study.