Peripheral quantitative computed tomography (pQCT) can assess bone geometric properties and separate cortical from trabecular bone. Despite pQCT's potential benefits for research, most reliability and accuracy studies have used a constant acquisition and analysis protocol. There are, however, numerous steps in the pQCT scan acquisition and analysis that are operator dependent. Whether or not these influence the quality of the pQCT scans and, potentially, the precision and validity of the data collected has been little explored. We investigated how pQCT outputs changed when operator-dependent parameters were varied, particularly when the bone of interest was of low mineral density. We found that bone parameters and scan failure rate varied significantly depending on the acquisition resolution; only one scan slice at the 10 and 30% radius is required to maintain adequate precision, and reference lines for sites should use a reproducible landmark. These results provide a foundation for recommending scan acquisition and analysis options for patients with low bone mass.