Purpose: Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. Methods: Fifteen healthy, recreationally active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomised sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Inter-individual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition interactions. Results: Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62 to 1.47, P < 0.001), and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the SD of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control adjusted exercise responses for all variables (r = 0.54 to 0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-by-condition interactions were present for all variables (P ≤ 0.053). Conclusion: Our replicated cross-over study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time.