A method of manufacturing a pipecolamide derivative, characterized in that pipecolic acid or an acid salt thereof is reacted with an amine in an inert solvent in the presence of a condensing agent such as dicyclohexylcarbodiimide, 1-ethyl-2-(2-dimethylaminopropyl)carbodiimide, methanesulfonyl chloride or phosphoryl chloride. Pipecolamide derivatives, particularly in optically active forms thereof can be efficiently and economically manufactured without harmful gas by-products.