A method for generating a population of tagged amplicons from target polynucleotides which are present in a nucleic acid sample, comprising the steps: a) forming a single reaction mixture containing: (i) a plurality of polynucleotides from the nucleic acid sample, and (ii) a plurality of oligonucleotide tags; b) generating within the single reaction mixture a plurality of tagged polynucleotides by appending at least one tag from the plurality of oligonucleotide tags to individual polynucleotides within the plurality of polynucleotides in a first and optionally subsequent enzymatic ligation reactions; c) generating a population of tagged amplicons by amplifying the plurality of tagged polynucleotides, d) sequencing at least some of the tagged amplicons to generate a plurality of candidate sequencing reads, including sequences corresponding to both a portion of the polynucleotide and a portion of the at least one oligonucleotide tag that is appended to the polynucleotide; wherein sequencing further comprises aligning sequence alignment anchors of the plurality of candidate sequencing reads; e) identifying a subset of candidate sequencing reads having errors; f) grouping the remaining candidate sequencing reads into families of grouped candidate sequencing reads having a common tag sequence that is unique to a given family of candidate sequencing reads; and g) removing mistagged sequencing reads from the families of candidate sequencing reads to produce error-corrected families of sequencing reads. wherein any two of the plurality of tagged polynucleotides are appended with tags that differ from each other, and wherein any two of the plurality of tagged polynucleotides are appended with a different oligonucleotide tag at both ends and wherein the oligonucleotide tag sequence comprises the structure N 1 N 2 N 3 X 1 X 2 X 3 or N 1 N 2 N 3 X 1 X 2 X 3 M 4 M 5 M 6 Y 4 Y 5 Y 6 (i) wherein "N" represents a random tag sequence wherein each base position in the random tag sequence is independently selected from A, G, C or T; (ii) wherein "X 1 X 2 X 3 " represents a fixed tag sequence that is the same in all of the plurality of tags; (iii) wherein "M" represents a random tag sequence wherein each base position in the random tag sequence is independently selected from A, G, C or T, wherein the random tag sequence "M" differs from the random tag sequence "N"; (iv) wherein "Y 4 Y 5 Y 6 " represents a fixed tag sequence that is the same in all of the plurality of tags, wherein the fixed tag sequence of "Y 4 Y 5 Y 6 " differs from the fixed tag sequence of "X 1 X 2 X 3 "; and wherein the fixed tag sequences "X 1 X 2 X 3 and Y 4 Y 5 Y 6 " are sequence alignment anchors. a) forming a single reaction mixture containing: (i) a plurality of polynucleotides from the nucleic acid sample, and (ii) a plurality of oligonucleotide tags; b) generating within the single reaction mixture a plurality of tagged polynucleotides by appending at least one tag from the plurality of oligonucleotide tags to individual polynucleotides within the plurality of polynucleotides in a first and optionally subsequent enzymatic ligation reactions; c) generating a population of tagged amplicons by amplifying the plurality of tagged polynucleotides, d) sequencing at least some of the tagged amplicons to generate a plurality of candidate sequencing reads, including sequences corresponding to both a portion of the polynucleotide and a portion of the at least one oligonucleotide tag that is appended to the polynucleotide; wherein sequencing further comprises aligning sequence alignment anchors of the plurality of candidate sequencing reads; e) identifying a subset of candidate sequencing reads having errors; f) grouping the remaining candidate sequencing reads into families of grouped candidate sequencing reads having a common tag sequence that is unique to a given family of candidate sequencing reads; and g) removing mistagged sequencing reads from the families of candidate sequencing reads to produce error-corrected families of sequencing reads. wherein any two of the plurality of tagged polynucleotides are appended with tags that differ from each other, and wherein any two of the plurality of tagged polynucleotides are appended with a different oligonucleotide tag at both ends and (i) wherein "N" represents a random tag sequence wherein each base position in the random tag sequence is independently selected from A, G, C or T; (ii) wherein "X 1 X 2 X 3 " represents a fixed tag sequence that is the same in all of the plurality of tags; (iii) wherein "M" represents a random tag sequence wherein each base position in the random tag sequence is independently selected from A, G, C or T, wherein the random tag sequence "M" differs from the random tag sequence "N"; (iv) wherein "Y 4 Y 5 Y 6 " represents a fixed tag sequence that is the same in all of the plurality of tags, wherein the fixed tag sequence of "Y 4 Y 5 Y 6 " differs from the fixed tag sequence of "X 1 X 2 X 3 "; and