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To test the hypothesis that daily acute intermittent hypoxia (AIH) combined with hand opening practice improves hand dexterity, function, and maximum hand opening in persons with chronic, motor-incomplete, cervical spinal cord injury.Six participants completed the double-blind, crossover study. Participants received daily (5 consecutive days) AIH (15 episodes per day: 1.5 minutes of fraction of inspired oxygen [FIO2] = 0.09, 1-minute normoxic intervals) followed by 20 repetitions of hand opening practice and normoxia (sham, FIO2 = 0.21) + hand opening practice. Hand dexterity and function were quantified with Box and Block and Jebsen-Taylor hand function tests. We also recorded maximum hand opening using motion analyses and coactivity of extensor digitorum and flexor digitorum superficialis muscles using surface EMG.Daily AIH + hand opening practice improved hand dexterity, function, and maximum hand opening in all participants. AIH + hand opening practice improved Box and Block Test scores vs baseline in 5 participants (p = 0.057) and vs sham + hand opening practice in all 6 participants (p = 0.016). All participants reduced Jebsen-Taylor Hand Function Test (JTHF) time after daily AIH + hand opening practice (−7.2 ± 1.4 seconds) vs baseline; 4 of 6 reduced JTHF time vs sham + hand opening practice (p = 0.078). AIH + hand opening practice improved maximum hand aperture in 5 of 6 participants (8.1 ± 2.7 mm) vs baseline (p = 0.018) and sham + hand opening practice (p = 0.030). In 5 participants, daily AIH–induced changes in hand opening were accompanied by improved EMG coactivity (p = 0.029).This report suggests the need for further study of AIH as a plasticity “primer” for task-specific training in spinal cord injury rehabilitation. Important clinical questions remain concerning optimal AIH dosage, patient screening, safety, and effect persistence.NCT01272336.