A green, convenient, high yielding and one-pot procedure for synthesis of high substituted dihydro-2-oxypyrroles by domino four-component condensation reaction between aromatic/aliphatic amines, dialkyl acetylenedicarboxylate and formaldehyde in the presence of a catalytic amount of caffeine as a green, natural, expedient and biodegradable catalyst under ambient temperature was studied. The salient features of this green approach are simplicity of operation and work-up procedures with no necessity of chromatographic purification steps, use of safe, non-volatile, non-corrosive and green catalyst, the availability and easy to handle of this solid catalyst, one-pot reaction, economical and clean synthesis. KEY WORDS: Caffeine, Green catalyst, Polysubstituted dihydro-2-oxypyrroles, Ambient temperature, Simple work-up Bull. Chem. Soc. Ethiop. 2019, 33(1), 149-158DOI: https://dx.doi.org/10.4314/bcse.v33i1.15