Reactions of N2O5 with protonated and deuterated water clusters X(+)(X(2)O)(n=3-30) X = H or D, were studied at temperatures ranging from 128 to 300 K and at pressures between 0.23 and 0.66 Torr using a fast-flow apparatus. For cluster ions with n greater than or equal to 5, the reaction X(+)(X(2)O)n + N2O5 --> X(+)(X(2)O)(n-1)XNO(3) + XNO(3) was observed to occur at temperatures below 150 K. At somewhat larger values of n which were acquired at temperatures about 130 K, the product ions X(+)(X(2)O)(n-2)(XNO(3))(2) and X(+)(X(2)O)(n-3)(XNO(3))(3) were also observed. The rate constants of the thermal energy reactions of N2O5 With X(+)(X(2)O)(n=5-21) were found to display both a size and pressure dependence. The present work gives the first experimental evidence for the reaction between large protonated water clusters (n greater than or equal to 5) and N2O5 under laboratory conditions, and the results provide further information for unraveling the chemistry of the upper atmosphere.