The aim of this study was to determine the effectiveness of a tailored footwear programme on lower-limb comfort in professional rugby league players. The study was conducted over 30 weeks and involved two professional teams (n = 59 players) from the Australian National Rugby League competition. One team was assigned to a footwear programme (intervention), while players from the control group continued usual practices of self-selected footwear. The tailored footwear programme consisting of player education, prescription of footwear, and frequent rotation of footwear resulted in a lower incidence of injury and higher comfort ratings. The intervention group had fewer lower-limb injuries (P = 0.005; Cohen d = 0.72) and higher comfort ratings (P < 0.001, Cohen d = 1.24) than the control group. Specifically, the intervention group reported a lower incidence of poor comfort events (mean = 3.8, s = 2.7) than the control group (mean = 7.9, s = 3.7). Observations also included fewer time loss events in the intervention (mean = 6.3, s = 4.8) than the control group (mean = 11.0, s = 6.3) and reduced injuries per 1000 h in the intervention (24.79/1000) than the control group (30.76/1000). These findings should help medical advisers improve footwear comfort in sportspeople and so reduce the incidence of related injuries.