This study reports a straightforward, metal-free, and acid-/base-free electrochemical C4-selective C–H deuteration of pyridine derivatives using D₂O at room temperature. The method is efficient, environmentally friendly, and offers high chemo- and regioselectivity, producing a wide range of deuterated compounds, including pyridines, quinolones, N-ligands, and biorelevant compounds. Mechanistic studies and cyclic voltammetry (CV) experiments demonstrate that N-butyl-2-phenylpyridinium iodide is a crucial intermediate in the electrochemical transformation. The protocol is versatile, with good to excellent deuterium incorporation and high yields for a variety of substrates, including aryl/alkyl-pyridines, quinolines, N-ligands, and biorelevant compounds. The electrochemical C–H deuteration is reversible and can be scaled up to gram quantities, making it a promising method for late-stage modification of biorelevant compounds.This study reports a straightforward, metal-free, and acid-/base-free electrochemical C4-selective C–H deuteration of pyridine derivatives using D₂O at room temperature. The method is efficient, environmentally friendly, and offers high chemo- and regioselectivity, producing a wide range of deuterated compounds, including pyridines, quinolones, N-ligands, and biorelevant compounds. Mechanistic studies and cyclic voltammetry (CV) experiments demonstrate that N-butyl-2-phenylpyridinium iodide is a crucial intermediate in the electrochemical transformation. The protocol is versatile, with good to excellent deuterium incorporation and high yields for a variety of substrates, including aryl/alkyl-pyridines, quinolines, N-ligands, and biorelevant compounds. The electrochemical C–H deuteration is reversible and can be scaled up to gram quantities, making it a promising method for late-stage modification of biorelevant compounds.