Home exercise programs (HEPs) are cost-effective and efficacious treatments for musculoskeletal pain conditions. Although HEPs are an important part of the continuum of care, non-adherence limits their effectiveness. The objective of this study was to examine adherence and specific barriers to clinician-prescribed HEPs in adults with musculoskeletal pain. A cross-sectional study was conducted with a total of 300patients presenting to an outpatient pain clinic in an academic medical center. Participants' self-reported information, including HEP completion frequency and barriers, was collected through a survey. The participants' mean age was 54.1 ± 15.8years (females = 133 (65.5%)). Of 203participants, 99 (48.8%) adhered to HEP, 56 (27.6%) partially adhered, and 48 (23.6%) did not adhere. One hundred eighty-seven (92.1%) participants reported receiving adequate instructions, and 175 (86.2%) reported receiving instructional materials. Age and "sufficient instructions" were found to be significant determinants of adherence (p< 0.05), while gender and handouts were not (p> 0.05). Pain in more than one body part was significantly (p< 0.05) associated with motivational barriers for non-adherence. Age and participants' perception of sufficient instructions were significant factors for non-adherence. These results emphasize the importance of therapist-provided instructions to overcome barriers to adherence.