The impact of ultramarathons (UM) on the organs, especially in professional athletes, is poorly understood. We tested a 36-year-old UM male runner before and after winning a 24-h marathon. The primary goal of the study was cardiovascular assessment. The athlete experienced right knee pain for the first time after 12 h of running (approximately 130 km), which intensified, affecting his performance. The competitors ran on a 1984 m rectangle-loop (950 × 42 m) in an atypical clockwise fashion. The winner completed 516 rectangular corners. Right knee Magnetic Resonance Imaging (MRI) one day after the run showed general overload in addition to degenerative as well as specific features associated with “turning to the right”. Re-examination after three years revealed none of these findings. Different kinds of overloading of the right lower limb, including right knee pain, were indicated in 6 of 10 competitors from the top 20, including a woman who set the world record. The affected competitors suggested as cause for discomfort the shape of the loop and running direction. They believed that changing the direction of the run during the competition and an athletics stadium loop shape on a 2000–2500 m length is better for 24-h UM runners. In the absence of technical alternatives, the “necessary evil” is a counterclockwise run (also Association of Athletics Federations IAAF recommendation). Results suggest that a one-way, clockwise, 24-h UM run had an adverse effect on the athlete’s right knee, as a result of unsymmetrical load. Organizers of 24-h UM runs should consider the shape of the competition loop and apply the principle of uniform load on the musculoskeletal system (alternate directions run). In case of technical impossibility, it would be better to run counterclockwise, which is more common, preferred by runners, and recommended by the IAAF.