Rugby league coaches adopt replacement strategies for their interchange players to maximize running intensity; however, it is important to understand the factors that may influence match performance.To assess the independent factors affecting running intensity sustained by interchange players during professional rugby league.Global positioning system (GPS) data were collected from all interchanged players (starters and nonstarters) in a professional rugby league squad across 24 matches of a National Rugby League season. A multilevel mixed-model approach was employed to establish the effect of various technical (attacking and defensive involvements), temporal (bout duration, time in possession, etc), and situational (season phase, recovery cycle, etc) factors on the relative distance covered and average metabolic power (Pmet) during competition. Significant effects were standardized using correlation coefficients, and the likelihood of the effect was described using magnitude-based inferences.Superior intermittent running ability resulted in very likely large increases in both relative distance and Pmet. As the length of a bout increased, both measures of running intensity exhibited a small decrease. There were at least likely small increases in running intensity for matches played after short recovery cycles and against strong opposition. During a bout, the number of collision-based involvements increased running intensity, whereas time in possession and ball time out of play decreased demands.These data demonstrate a complex interaction of individual- and match-based factors that require consideration when developing interchange strategies, and the manipulation of training loads during shorter recovery periods and against stronger opponents may be beneficial.