A method for determining the fraction of fetal nucleic acids in a maternal blood sample comprising a mixture of fetal and maternal genomic DNA, wherein said fetal and maternal genomic DNA is cell-free DNA (cfDNA), said method comprising: (a) amplifying a plurality of polymorphic target nucleic acids in said mixture, wherein each amplified polymorphic target nucleic acid comprises at least one polymorphic site, using primer pairs each capable of amplifying a target nucleic acid sequence comprising a polymorphic site in a multiplex PCR reaction, to generate a panel of amplified polymorphic sites that contains a sufficient number of polymorphic sites such that at least 25 are informative polymorphic sites; (b) performing massively parallel sequencing of at least a portion of the amplified product obtained in (a), wherein said sequencing comprises providing a plurality of sequence tags for said panel of amplified polymorphic sites; and (c) using said plurality of sequence tags to: (i) identify at least one informative polymorphic site in said panel of amplified polymorphic sites, wherein said at least one informative polymorphic site is identified by the difference in the allelic sequences at each polymorphic site and the number of sequence tags mapped to each of the possible alleles at each polymorphic site, and (ii) determine said fraction of fetal nucleic acids by using the total number of tags that map to a first allele at an identified informative polymorphic site and the total number of tags that map to a second allele at the identified informative polymorphic site to calculate said fraction of fetal nucleic acids. (a) amplifying a plurality of polymorphic target nucleic acids in said mixture, wherein each amplified polymorphic target nucleic acid comprises at least one polymorphic site, using primer pairs each capable of amplifying a target nucleic acid sequence comprising a polymorphic site in a multiplex PCR reaction, to generate a panel of amplified polymorphic sites that contains a sufficient number of polymorphic sites such that at least 25 are informative polymorphic sites; (b) performing massively parallel sequencing of at least a portion of the amplified product obtained in (a), wherein said sequencing comprises providing a plurality of sequence tags for said panel of amplified polymorphic sites; and (c) using said plurality of sequence tags to: (i) identify at least one informative polymorphic site in said panel of amplified polymorphic sites, wherein said at least one informative polymorphic site is identified by the difference in the allelic sequences at each polymorphic site and the number of sequence tags mapped to each of the possible alleles at each polymorphic site, and (ii) determine said fraction of fetal nucleic acids by using the total number of tags that map to a first allele at an identified informative polymorphic site and the total number of tags that map to a second allele at the identified informative polymorphic site to calculate said fraction of fetal nucleic acids. (i) identify at least one informative polymorphic site in said panel of amplified polymorphic sites, wherein said at least one informative polymorphic site is identified by the difference in the allelic sequences at each polymorphic site and the number of sequence tags mapped to each of the possible alleles at each polymorphic site, and (ii) determine said fraction of fetal nucleic acids by using the total number of tags that map to a first allele at an identified informative polymorphic site and the total number of tags that map to a second allele at the identified informative polymorphic site to calculate said fraction of fetal nucleic acids.