Regioselective hydrogenation of the oxidized form of beta-nicotinamide adenine dinucleotide (NAD(+)) to the reduced form (NADH) with hydrogen (H-2) has successfully been achieved in the presence of a catalytic amount of a [C,N] cyclometalated organoiridium complex [Ir-III(Cp*)(4-(1H-pyrazol-1-yl-kappa N-2)benzoic acid-kappa C-3)(H2O)](2) SO4 [1](2)center dot SO4 under an atmospheric pressure of H-2 at room temperature in weakly basic water. The structure of the corresponding benzoate complex Ir-III(Cp*)(4-(1H-pyrazol-1-yl-kappa N-2)-benzoate-kappa C-3)(H2O) 2 has been revealed by X-ray single-crystal structure analysis. The corresponding iridium hydride complex formed under an atmospheric pressure of H-2 undergoes the 1,4-selective hydrogenation of NAD(+) to form 1,4-NADH. On the other hand, in weakly acidic water the complex 1 was found to catalyze the hydrogen evolution from NADH to produce NAD(+) without photoirradiation at room temperature. NAD(+) exhibited an inhibitory behavior in both catalytic hydrogenation of NAD(+) with H-2 and H-2 evolution from NADH due to the binding of NAD(+) to the catalyst. The overall catalytic mechanism of interconversion between NADH and NAD(+) accompanied by generation and consumption of H-2 was revealed on the basis of the kinetic analysis and detection of the catalytic intermediates.