A method for determining the presence or absence of a fetal aneuploidy in a maternal sample comprising a mixture of fetal and maternal nucleic acid molecules, wherein the maternal sample is a plasma sample and wherein said fetal and maternal nucleic acid molecules are cell-free DNA (cfDNA) molecules, said method comprising: (a) preparing a sequencing library from said mixture; wherein preparing said library comprises the consecutive steps of end-repairing, dA-tailing and adaptor ligating said fetal and maternal nucleic acid molecules, and wherein said consecutive steps exclude purifying the end-repaired products prior to the dA-tailing step and exclude purifying the dA-tailing products prior to the adaptor-ligating step; (b) sequencing at least a portion of the nucleic acid molecules in the sequencing library by massively parallel sequencing, thereby obtaining sequence information for a plurality of fetal and maternal nucleic acid molecules of the maternal sample, wherein the sequence information comprises sequence reads; and (c) using the sequence information to determine the presence or absence of a fetal aneuploidy in the maternal sample, wherein using the sequence information to determine the presence or absence of a fetal aneuploidy in the maternal sample comprises: (i) aligning the sequence reads to a human reference genome and counting as mapped sequence tags the reads that are uniquely mapped to the human reference genome; (ii) counting the mapped sequence tags to determine the sequence tag density for a sequence of interest and for at least one normalizing sequence; (iii) determining a sequence dose for the sequence of interest using the number of mapped sequence tags for the sequence of interest and the number of mapped sequence tags for the at least one normalizing sequence; (iv) comparing said dose to a threshold value, wherein the threshold value is a number that serves as a limit of diagnosis of an aneuploidy, and thereby identifying the presence or absence of a fetal aneuploidy in the maternal sample. (a) preparing a sequencing library from said mixture; wherein preparing said library comprises the consecutive steps of end-repairing, dA-tailing and adaptor ligating said fetal and maternal nucleic acid molecules, and wherein said consecutive steps exclude purifying the end-repaired products prior to the dA-tailing step and exclude purifying the dA-tailing products prior to the adaptor-ligating step; (b) sequencing at least a portion of the nucleic acid molecules in the sequencing library by massively parallel sequencing, thereby obtaining sequence information for a plurality of fetal and maternal nucleic acid molecules of the maternal sample, wherein the sequence information comprises sequence reads; and (c) using the sequence information to determine the presence or absence of a fetal aneuploidy in the maternal sample, wherein using the sequence information to determine the presence or absence of a fetal aneuploidy in the maternal sample comprises: (i) aligning the sequence reads to a human reference genome and counting as mapped sequence tags the reads that are uniquely mapped to the human reference genome; (ii) counting the mapped sequence tags to determine the sequence tag density for a sequence of interest and for at least one normalizing sequence; (iii) determining a sequence dose for the sequence of interest using the number of mapped sequence tags for the sequence of interest and the number of mapped sequence tags for the at least one normalizing sequence; (iv) comparing said dose to a threshold value, wherein the threshold value is a number that serves as a limit of diagnosis of an aneuploidy, and thereby identifying the presence or absence of a fetal aneuploidy in the maternal sample. (i) aligning the sequence reads to a human reference genome and counting as mapped sequence tags the reads that are uniquely mapped to the human reference genome; (ii) counting the mapped sequence tags to determine the sequence tag density for a sequence of interest and for at least one normalizing sequence; (iii) determining a sequence dose for the sequence of interest using the number of mapped sequence tags for the sequence of interest and the number of mapped sequence tags for the at least one normalizing sequence; (iv) comparing said dose to a threshold value, wherein the threshold value is a number that serves as a limit of diagnosis of an aneuploidy, and thereby identifying the presence or absence of a fetal aneuploidy in the maternal sample.