Ruthenium pyrochlores, that is, oxides of composition A(2)Ru(2)O(7-delta), have emerged recently as state-of-the-art catalysts for the oxygen evolution reaction (OER) in acidic conditions. Here, we demonstrate that the A-site substituent in yttrium ruthenium pyrochlores Y1.8M0.2Ru2O7-delta (M = Cu, Co, Ni, Fe, Y) controls the concentration of surface oxygen vacancies (V-O) in these materials whereby an increased concentration of V-O sites correlates with a superior OER activity. DFT calculations rationalize these experimental trends demonstrating that the higher OER activity and V-O surface density originate from a weakened strength of the M-O bond, scaling with the formation enthalpy of the respective MOx phases and the coupling between the M d states and O 2p states. Our work introduces a novel catalyst with improved OER performance, Y1.8M0.2Ru2O7-delta, and provides general guidelines for the design of active electrocatalysts.