The paper presents the results of experimental studies on the impact of impulse shot peening parameters on surface roughness (Sa, Sz, Sp, Sv), surface layer microhardness, and the mean positron lifetime (τmean). In the study, samples made of the Inconel 718 nickel alloy were subjected to impulse shot peening on an originally designed stand. The variable factors of the experiment included the impact energy, the diameter of the peening element, and the number of impacts per unit area. The impulse shot peening resulted in changes in the surface structure and an increase in surface layer microhardness. After the application of impulse shot peening, the analyzed roughness parameters increased in relation to post-milling values. An increase in microhardness was obtained, i.e., from 27 HV 0.05 to 108 HV 0.05 at the surface, while the maximum increase the microhardness occur at the depth from 0.04 mm to 0.08 mm. The changes in the physical properties of the surface layer were accompanied by an increase in the mean positron lifetime τmean. This is probably related to the increased positron annihilation in point defects. In the case of small surface deformations, the increase in microhardness was accompanied by a much lower increase in τmean, which may indicate a different course of changes in the defect structure consisting mainly in modification of the dislocation system. The dependent variables were subjected to ANOVA analysis of variance (it was one-factor analysis), and the effect of independent variables was evaluated using post-hoc tests (Tukey test).