Peripheral quantitative computed tomography (pQCT) can be used to examine bone strength outcomes and muscle size and fatty infiltration. Our research team and others have used it to examine bone loss after spinal cord injury (SCI). However, the high prevalence of restricted lower extremity range of motion, spasticity, edema, excessive muscle atrophy, or severe osteoporosis necessitates changes to standard protocols for screening, positioning during scan acquisition, and analysis methods. This manuscript outlines the challenges that we experienced using pQCT in individuals with SCI, and provides solutions, ones that may also be applicable when using pQCT in individuals with other chronic conditions or in older adults. Suggestions for participant screening, positioning individuals for scanning while in a wheelchair, scan site selection, need for attendant assistance, and considerations in the presence of secondary complications, such as contracture, spasticity, and paralysis, are presented. In the presence of very low bone mineral density or severe muscle atrophy, the default analysis modes provided by the manufacturer may not provide valid estimates of bone or muscle indices; we propose alternates. We have used watershed segmentation methods to determine muscle size and density based on lower precision error compared to threshold-based edge-detection segmentation, particularly for adults with SCI, where more fatty infiltration was present. By presenting our "lessons learned," we hope to reduce the learning curve for researchers using pQCT in the future.