Spinal cord injury leads to a pronounced reduction of cardiovascular, pulmonary, and metabolic ability. Physical activity, up to and including high-performance sports, has obtained importance in the course of rehabilitation and the postclinical phase. Thirteen elite female wheelchair basketball players from the German National Basketball Team and 10 female sedentary spinal cord-injured persons were examined in the study. Heart volume was measured by an echocardiography. All subjects underwent a graded exercise test on a wheelchair ergometer. Additionally, heart rate, lactate, and player points were measured during a competitive basketball game in wheelchair basketball players. Cardiac dimensions were larger for spinal cord-injured wheelchair basketball players (620.3 ml; 9.6 ml · kg−1) in comparison with spinal cord-injured persons (477.4 ml; 8.2 ml · kg−1) but did not exceed the heart volume of untrained nonhandicapped persons. In contrast, athletes with amputations or those having had poliomyelitis reached training-induced cardiac hypertrophy in relation to body mass (713.7 ml; 13.2 ml · kg−1), as observed in nonhandicapped athletes. During graded wheelchair ergometry, wheelchair basketball players showed a higher maximal work rate (59.9 v 45.5 W), maximal oxygen consumption (33.7 v 18.3 ml · min−1 · kg−1), and maximal lactate (9.1 v 5.47 mmol · l−1) without a difference in maximal heart rate and workload at AT4 than did spinal cord-injured persons. The average heart rate during the wheelchair basketball game was 151 · min−1, and the lactate concentration was 1.92 mmol · l−1. Female athletes with a less severe handicap and higher maximal oxygen consumption during the graded exercise test reached a higher game level in the evaluation. During the competitive basketball game, high cardiovascular stress was observed, indicating a fast aerobic metabolism; the anaerobic lactic acid capacity played a subordinate role. Wheelchair basketball is an effective and suitable sport to enhance physical performance and to induce positive physiological adaptations.