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The organic cofactor riboflavin is shown to serve as a cost-effective and atom-efficient source of reducing equivalents to support biocatalytic alkene reductions catalyzed by ene-reductase enzymes, when integrated with either a H₂-driven or an electrochemical recycling system. The robust NiFe hydrogenase from Escherichia coli, Hyd1, is employed for the H₂-driven reduction of riboflavin, and unmediated electrochemical recycling of reduced riboflavin at a simple carbon electrode is also demonstrated. It is further shown that H₂-driven riboflavin reduction can be implemented in continuous flow using a packed-bed reactor containing Hyd1 immobilized on a carbon support. These findings highlight that the expensive nicotinamide cofactors, NADH or NADPH, can be replaced by riboflavin for ene-reductase applications in biotechnology, in both batch and continuous flow systems, as well as in electrosynthesis.