Using acetal-stabilized lignin we performed a truly steady state continuous high-yielding lignin depolymerization (45% monophenolics using Ni/C), which offered a window into challenges and opportunities that will be faced when processing this feedstock. With an excess of catalyst present, we observed stable depolymerization yields for 125 h time on stream. However, using catalyst loadings that were just sufficient to achieve initial maximum hydrogenolysis monomer yields revealed rapid catalyst deactivation. High yields could be partially recovered with high temperature regeneration under a reducing environment. Characterization of spent catalysts revealed that sintering and carbonaceaous deposits rather than leaching were the main phenomena causing deactivation.