<jats:p> Strenuous exercise increases gastrointestinal damage, but the dose–response relationship is yet to be elucidated. It is also commonly believed that running causes greater gastrointestinal damage than cycling. Two randomised, crossover studies aimed to 1) quantify gastrointestinal damage with increasing exercise intensity, and 2) determine if running was associated with greater gastrointestinal damage than cycling. Following a maximal oxygen uptake (V̇O<jats:sub>2max</jats:sub>) test, participants completed 3 cycling trials at different intensities (60 min at 40%, 60% and 80% V̇O<jats:sub>2max</jats:sub>; n = 10 (5 female, 5 male)) (INTENSITY), or 1 running and 1 cycling trial (45 min at 70% V̇O<jats:sub>2max</jats:sub>; n = 11 (3 female, 8 male)) (MODE). Venous blood samples were collected pre- and post-exercise to measure gastrointestinal damage via intestinal fatty acid binding protein (I-FABP). In INTENSITY, I-FABP magnitude of change was greater at 80% V̇O<jats:sub>2max</jats:sub> than 40% V̇O<jats:sub>2max</jats:sub> (p < 0.01). In MODE, I-FABP magnitude of change was greater with cycling (mean (SD)) (84.7 (133.2)% d = 1.07) compared with running (19.3 (33.1)%, d = 0.65) with a moderate effect (d = 0.68, p = 0.024). Rating of perceived exertion (RPE) and heart rate (HR) were higher during cycling (RPE p < 0.0001; HR p < 0.0001) but rectal temperature was not different between modes (p = 0.94). While gastrointestinal damage increases with increasing exercise intensity, running was not associated with greater gastrointestinal damage than cycling. </jats:p><jats:p> Novelty: A fraction of the anaerobic threshold, rather than a fraction of V̇O<jats:sub>2max</jats:sub>, may be more predictive of intensity that results in exercise induced gastrointestinal damage. The mode of exercise may not be as important as intensity for inducing gastrointestinal damage. Improving anaerobic threshold may reduce susceptibility to gastrointestinal damage when exercising at high intensities. </jats:p>