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C1-Esterase Inhibitor (C1-INH) is a protein present in human plasma and is a member of serine protease inhibitors super family. C1-INH is a molecule with lot of therapeutic importance and is widely used in the treatment of Angioedema and in the current research an improved purification scheme is developed to fractionate C1-INH from human plasma. By a series of chromatography steps C1-INH is purified to homogeneity. A simple three step chromatography procedure has been described excluding the more inefficient or cumbersome methods like precipitation or affinity capture. The C1-INH purified by this scheme is characterized along with the reference molecule. C1-INH produced by this method is a single-chain glycoprotein with a molecular weight of 85-93 KDa with increased purity and yields of 100-120 mg/L of plasma. The chromatography steps are easily scalable and the process is economical and adaptable for therapeutic protein manufacture.