Hierarchically structured IO-TiO2 electrodes were fabricated on Ti foil via a co-assembly method adapted for thick films of 37 µm (geometric surface area = 0.19 cm 2 ). Polystyrene beads (750 nm) served as a sacrificial template, forming post-annealing macropores (~660 nm) supported by a mesoporous TiO2 nanoparticle (~20 nm) skeleton (Fig. ,e and Fig. ). The IO-TiO2 electrode has a roughness factor of ~130 (Fig. ), forms a robust biocompatible interface (see successive protein film voltammetry, PFV, in Fig. ) and provides a high loading of enzymes with good electrochemical stability at cathodic potentials (see Fig. for comparison with less stable mesoporous ITO). H2ase and FDH from Desulfovibrio vulgaris Hildenborough (DvH) were chosen for their excellent H + /CO2 reduction activities and significant tolerance to small amounts of O2 , suitable for application in a semi-artificial leaf coupled to H2O oxidation.