Cu-catalyzed azide-alkyne cycloaddition reaction in aqueous medium was dramatically accelerated by a simple zwitterionic additive, betaine, at ambient temperature. In the presence of betaine, 1,4-disubstituted1,2,3- triazoles were obtained from azides and terminal alkynes in excellent yields under 2.5-200 ppm levels of Cu-(I) in water. This method resulted in the remarkable reduction of the Cu-(I) concentration down to ppm levels. The advantages of this protocol include the use of a conventional Cu catalytic system with commercially available betaine, which is generally non-toxic for biological application. Therefore, this efficient catalytic system should have broad applications in life science research and materials science.