A double stranded RNAi agent capable of inhibiting the expression of Proprotein convertase subtilisin kexin 9 (PCSK9) in a cell, wherein said double stranded RNAi agent comprises: (a) a sense strand complementary to an antisense strand, wherein said antisense strand comprises a region complementary to part of an mRNA encoding PCSK9, wherein each strand is about 17 to about 30 nucleotides in length, wherein said antisense strand comprises at least 17 nucleotides from the nucleobase sequence ACAAAAGCAAAACAGGUCUAG (SEQ ID NO: 412) and the double stranded RNAi agent is represented by formula: wherein: i, j, k, and I are each independently 0 or 1; p, p', q, and q' are each independently 0-6; each N a and N a ' independently represents an oligonucleotide sequence comprising 0-25 nucleotides which are either modified or unmodified or combinations thereof, each sequence comprising at least two differently modified nucleotides; each N b and N b ' independently represents an oligonucleotide sequence comprising 0-10 nucleotides which are either modified or unmodified or combinations thereof; each n p, n p ', n q, and n q ', each of which may or may not be present, independently represents an overhang nucleotide; XXX, YYY, ZZZ, X'X'X', Y'Y'Y', and Z'Z'Z' each independently represent one motif of three identical modifications on three consecutive nucleotides; modifications on N b differ from the modification on Y and modifications on N b ' differ from the modification on Y; wherein the modifications on the nucleotides are 2'-O-methyl or 2'-fluoro modifications; and wherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker; or (b) an antisense strand consisting of the nucleotide sequence asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa and a sense strand consisting of the nucleotide sequence csusagacCfuGfudTuugcuuuugu, wherein a, g, c, and u are 2'-O-methyl (2'-OMe) modified A, G, C, and U nucleotides, respectively; Af, Gf, Cf and Uf are 2'-fluoro A, G, C and U modified nucleotides, respectively; dT is a deoxy-thymine nucleotide and s is a phosphorothioate linkage; and wherein the sense strand is conjugated to at least one ligand. (a) a sense strand complementary to an antisense strand, wherein said antisense strand comprises a region complementary to part of an mRNA encoding PCSK9, wherein each strand is about 17 to about 30 nucleotides in length, wherein said antisense strand comprises at least 17 nucleotides from the nucleobase sequence ACAAAAGCAAAACAGGUCUAG (SEQ ID NO: 412) and the double stranded RNAi agent is represented by formula: wherein: i, j, k, and I are each independently 0 or 1; p, p', q, and q' are each independently 0-6; each N a and N a ' independently represents an oligonucleotide sequence comprising 0-25 nucleotides which are either modified or unmodified or combinations thereof, each sequence comprising at least two differently modified nucleotides; each N b and N b ' independently represents an oligonucleotide sequence comprising 0-10 nucleotides which are either modified or unmodified or combinations thereof; each n p, n p ', n q, and n q ', each of which may or may not be present, independently represents an overhang nucleotide; XXX, YYY, ZZZ, X'X'X', Y'Y'Y', and Z'Z'Z' each independently represent one motif of three identical modifications on three consecutive nucleotides; modifications on N b differ from the modification on Y and modifications on N b ' differ from the modification on Y; wherein the modifications on the nucleotides are 2'-O-methyl or 2'-fluoro modifications; and wherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker; or i, j, k, and I are each independently 0 or 1; p, p', q, and q' are each independently 0-6; each N a and N a ' independently represents an oligonucleotide sequence comprising 0-25 nucleotides which are either modified or unmodified or combinations thereof, each sequence comprising at least two differently modified nucleotides; each N b and N b ' independently represents an oligonucleotide sequence comprising 0-10 nucleotides which are either modified or unmodified or combinations thereof; each n p, n p ', n q, and n q ', each of which may or may not be present, independently represents an overhang nucleotide; XXX, YYY, ZZZ, X'X'X', Y'Y'Y', and Z'Z'Z' each independently represent one motif of three identical modifications on three consecutive nucleotides; modifications on N b differ from the modification on Y and modifications on N b ' differ from the modification on Y; wherein the modifications on the nucleotides are 2'-O-methyl or 2'-fluoro modifications; and wherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker; or (b) an antisense strand consisting of the nucleotide sequence asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa and a sense strand consisting of the nucleotide sequence csusagacCfuGfudTuugcuuuugu, wherein a, g, c, and u are 2'-O-methyl (2'-OMe) modified A, G, C, and U nucleotides, respectively; Af, Gf, Cf and Uf are 2'-fluoro A, G, C and U modified nucleotides, respectively; dT is a deoxy-thymine nucleotide and s is a phosphorothioate linkage; and wherein the sense strand is conjugated to at least one ligand.