To evaluate match performances of substitute players using different research designs. English Premier League matches were analyzed using a multiple-camera system. Two research designs were adopted: an independent-measures analysis comparing the match-performance characteristics of players completing the entire match (n = 810) vs substitutes (n = 286) and the players they replaced (n = 286) and a repeated-measures analysis comparing the same players completing full matches vs those in which they were introduced as a substitute (n = 94). Most substitutions (P < .05) occurred at halftime and between the 60- to 85-min vs all first-half periods and the remaining second-half periods (effect size ES: 0.85-1.21). These substitutions become more (P < .01) offensive (eg, more attacking positions were introduced) in relation to the positions introduced as the half progressed (ES: 0.93-1.37). Independent-measures analysis indicated that high-intensity running was greater (P < .01) in substitutes compared with players who either completed the entire match or were replaced (ES: 0.28-0.67), but no differences were evident for pass-completion rates (ES: 0.01-0.02). Repeated-measures analysis highlighted that players covered more (P < .01) high-intensity running when they were introduced as substitutes compared with the equivalent period of the second- but not the first-half period (ES: 0.21-0.47). Both research designs indicated that attackers covered more (P < .05) high-intensity running than peers or their own performances when completing the entire match (ES: 0.45- 0.71). Substitutes cover greater high-intensity-running distance; this was particularly evident in attackers, but pass-completion rates did not differ for any position. This information could be beneficial to coaches regarding optimizing the match running performances of their players, but much more work needs to be undertaken to investigate the overall impact of substitutes (physical, technical indicators, and contribution to key moments of matches).