Abstract Purpose Vertebral compression fractures (VCFs) are common and associated with high morbidity including severe, debilitating pain. Percutaneous vertebroplasty/kyphoplasty is a demonstrated effective treatment for VCF. Sarcopenia has been implicated as a risk factor for VCF and refracture following cement augmentation, and as a risk factor for procedural complications in some populations; however, the effect of sarcopenia on VCF patients undergoing these procedures is unknown. This study aims to improve outcomes and patient selection by investigating the effects of highly common VCF comorbidities. Methods A retrospective study was performed of all patients who underwent vertebroplasty/kyphoplasty for treatment of VCF at a single center from 2007 to 2020. Sarcopenia was quantified by normalized total psoas area (TPA) as measured on computed tomography. The effect of sarcopenia, bone density t-score, and clinical and demographic covariates on periprocedural pain scores was evaluated with linear mixed-effects models. Results Out of 458 procedures performed, 146 and 130 were included in the sarcopenia and osteoporosis analyses, respectively. Sarcopenia and osteoporosis were highly comorbid in VCF patients undergoing vertebroplasty/kyphoplasty. Linear mixed-effects modeling showed no significant association between change in pain score and TPA score (p = 0.827) or bone density t-score (p = 0.818). Conclusion Postprocedural pain reduction after vertebroplasty/kyphoplasty is not associated with the presence or severity of sarcopenia or osteoporosis/osteopenia. Appropriate patient selection remains critical to optimize the risk–benefit ratio of vertebroplasty/kyphoplasty, and sarcopenia and osteoporosis should not be considered contraindications to these procedures.