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Hydrogen isotopically labeled compounds have extensive utility across diverse domains, especially in drug discovery and development. However, synthesis of the labeled compounds with exclusive site selectivity and/or high isotope incorporation is challenging. One widely employed method is heterogeneous palladium(0)-catalyzed (such as Pd/C) dehalogenative deuteration and tritiation with D2/T2gas. While commonly used, the method faces two long-standing challenges related to insufficient isotope incorporation and functional group tolerance, particularly with aryl bromides and chlorides. These long-standing issues pose a substantial obstacle in the synthesis of deuterated drug molecules and high-specific-activity tritium tracers. Herein, we present a novel palladium catalytic system using Zn(OAc)2as an additive, enabling novel homogenous dehalogenative deuteration/tritiation using D2/T2gas. Under mild reaction conditions, a wide range of drug-like aryl halides and pseudohalides undergo selective deuteration with complete isotope incorporation. The reaction displays excellent compatibility with diverse functional groups, including multiple bonds and O/N-benzyl, and cyano groups, which are frequently problematic in the Pd/C reactions. Furthermore, this method was successfully applied to the tritiation of four halogenated pharmaceutically relevant molecules, resulting in predictable high specific activity per halogen atom (26.5–27.7 Ci/mmol). Notably, the developed system allows gram-scale preparation of a deuterium-containing intermediate, a crucial step in synthesizing a deuterium-labeled drug molecule. A key intermediate, Pd(Ar)OAc, is proposed to activate hydrogen gas during dehalogenative deuteration and tritiation, and Zn(OAc)2plays an essential role in inhibiting Pd poisoning by halides.