Abstract: A method for producing bivalirudin using solid phase peptide synthesis by the following steps: a) mixing a Fmoc-amino acid resin or a Fmoc-peptide resin with a de-protective agent so as to remove Fmoc-; b) in the presence of a condensing agent, condensing a Fmoc- or Boc-amino acid with the amino acid or the peptide bound to the resin; c) repeating the steps a) and b) to yield a peptide resin represented by Formula I, (SEQ?ID?NO.?1) Boc-D-Phe1-Pro2-Arg(Pbf)3-Pro4-Gly5-Gly6-Gly7- Gly8-Asn(Trt)9-Gly10-Asp(OtBu)11-Phe12-Glu (OtBu)13-Glu(OtBu)14-Ile15-Pro16-Glu(OtBu)17-Glu (OtBu)18-Tyr(tBu)19-Leu20-Resin?(I) and d) in the presence of a cleavage agent, separating the peptide from the resin to yield bivalirudin represented by Formula II (SEQ ID NO. 2). D-Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe- Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu?(II) Based on its total volume, the de-protective agent is composed of between 3 and 20% of piperidine and between 0.