Objective: The effect of ultra-long distance running on the ankle cartilage with regard to biochemical changes, thickness and lesions is examined in the progress of a transcontinental ultramarathon over 4486km. Method: In an observational field study, repeated follow-up scanning of 22 participants of the TransEurope FootRace (TEFR) with a 1.5T MRI mounted on a mobile unit was performed. For quantitative biochemical and structural evaluation of cartilage a fast low angle shot (FLASH) T2* weighted gradient-echo (GRE)-, a turbo-inversion-recovery-magnitude (TIRM)- and a fat-saturated proton density (PD)-weighted sequence were utilized. Statistical analysis of cartilage T2* and thickness changes was obtained on the 13 finishers (12 male, mean age 45.4 years, BMI 23.5kg/m2). None of the nine non-finisher (eight male, mean age 53.8 years, BMI 23.4kg/m2) stopped the race due to ankle problems. Results: From a mean of 17.0ms for tibial plafond and 18.0ms for talar dome articular cartilage at baseline, nearly all observed regions of interest (ROIs) of the ankle joint cartilage showed a significant T2*-signal increase (25.6% in mean), with standard error ranging from 19% to 33% within the first 2500km of the ultra-marathon. This initial signal behavior was followed by a signal decrease. This signal recovery (30.6% of initial increase) showed a large effect size. No significant morphological or cartilage thickness changes (at baseline 2.9mm) were observed. Conclusion: After initial T2*-increase during the first 2000-2500km, a subsequent T2*-decrease indicates the ability of the normal cartilage matrix to partially regenerate under ongoing multistage ultramarathon burden in the ankle joints.