Argatroban, an antithrombotic drug, was synthesized from (2R,4R)-4-methylpiperidine-2-carboxylic acid via esterification, condensation with (S)-2-[(tert-butoxycarbonyl) amino]-5-(3-nitroguanidino)pentanoic acid, deprotection of Boc group, condensation with 3-methylquinoline-8-sulfonyl chloride, hydrolysis, Pd/C-catalyzed hydrogenation and simultaneous deprotection, and purification with an overall yield about 12% and a purity of 99.5%. This method was suitable for industrialization because of its simple operation and stable process.