We measured intramuscular oxygenation in the anterior tibial muscle of 176 patients with exercise-induced leg pain by noninvasive near-infrared spectroscopy before, during, and after an exercise test that elicited the symptoms. Clinical investigation was performed after each test. Intramuscular pressure was measured in patients with nonconclusive findings. Chronic anterior compartment syndrome (CACS) was diagnosed in 47 patients, and other causes for the leg pain were diagnosed in 129 patients by clinical means. The mean level of oxygenation decreased to 33 ± 19% in patients with CACS and to 34 ± 19% in patients without CACS compared with baseline level (100%) at rest before exercise. The level of oxygenation was below 20% during the exercise test in 12 of 47 (26%) patients with CACS and in 30 of 129 (23%) patients without CACS. The time required for reoxygenation after the cessation of exercise was 61 ± 34 s in patients with CACS and 46 ± 20 s in patients without CACS (P < 0.05). We conclude that the magnitude of intramuscular deoxygenation during exercise is an unreliable measure to diagnose CACS. However, the time for reoxygenation returning to baseline level following an exercise test is a valuable adjunct in diagnosing CACS.