Gastin, PB, Hunkin, SL, Fahrner, B, and Robertson, S. Deceleration, acceleration, and impacts are strong contributors to muscle damage in professional Australian football. J Strength Cond Res 33(12): 3374-3383, 2019-The purpose of this study was to investigate the relationships between serum creatine kinase [CK], an indirect marker of muscle damage, and specific indices of match load in elite Australian football. Twenty-six professional players were assessed during a competitive Australian Football League (AFL) season. [CK] was collected 24-36 hours before match and 34-40 hours after match during 8 in-season rounds. An athlete-tracking technology was used to quantify match load. Generalized estimating equations and random forest models were constructed to determine the extent to which match-load indices and pre-match [CK] explained post-match [CK]. There was a 129 ± 152% increase in [CK] in response to AFL competition. Generalized estimating equations found that number of impacts >3g (p = 0.004) and game time (p = 0.016) were most strongly associated with post-match [CK]. Random forest, with considerably lower errors (130 vs. 316 U·L), found deceleration, acceleration, impacts >3g, and sprint distance to be the strongest predictors. Pre-match [CK] accounted for 11% of post-match [CK], and considerable interindividual and intraindividual variability existed in the data. Creatine kinase, an indicator of muscle damage, was considerably elevated as a result of AFL competition. Parametric and machine-learning analysis techniques found several indices of physical load associated with muscle damage during competition, with impacts >3g and high-intensity running variables as the strongest predictors. [CK] may be used as a global measure of muscle damage in field team sports such as AF, yet with some caution given cost, invasiveness, and inherent variability. Quantifying physical load and the responses to that load can guide athlete management decision-making and is best undertaken within a suite of practical, sport-specific measures, where data are interpreted individually and with an understanding of the limitations.