As a starting point for evaluating a broader range of conditions for H2 oxidation complexes, in this work we investigate an efficient and reversible Ni-based H2 oxidation and production complex with an arginine in the outer coordination sphere, [Ni(P(Cy)2N(Arginine)2)2](7+) (CyArg). We tested this complex under a wide range of pressures and temperatures, in two different solvents (methanol and water), to determine if simultaneous improvements in rate and overpotential could be achieved. We found that the optimal conditions combined both high temperature (72 °C) and pressure (100 atm H2) in acidic aqueous solution (pH = 1), resulting in the fastest H2 oxidation reported for any homogeneous electrocatalyst to date (TOF 1.1 × 10(6) s(-1)) operating at 240 mV overpotential. The activation free energy in water was determined to be 10 kcal mol(-1) at all pressures studied. Surprisingly, in methanol under the same temperature and pressure, CyArg had a TOF for H2 oxidation of only 280 s(-1) at an overpotential of 750 mV. Comparisons to the data in water, and to a control complex, [Ni(P(Cy)2N(Benzyl)2)2](2+) (CyBn; Bn = benzyl), suggest that this substantial difference is likely due to a change in rate limiting step from H2 addition to deprotonation. Importantly, the optimal conditions we identified for CyArg (elevated temperature and acidic aqueous solutions), are amenable to fuel cell technologies and provide an important advancement in implementing homogeneous synthetic catalysts for renewable energy.