Introduction: Factors that motivate musculoskeletal patients to pursue an intensive, lifestyle medicine–based approach to care are poorly understood. Objective: To determine whether, compared to patients seeking musculoskeletal care through traditional pathways, patients who choose an intensive lifestyle medicine program for musculoskeletal pain endorse greater physical dysfunction, worse psychological health, and/or more biopsychosocial comorbidities. Design: Cross-sectional analysis of existing medical records from 2018 to 2021. Setting: Orthopedic department of one academic medical center. Patients: Fifty consecutive patients who enrolled in an intensive lifestyle medicine program to address a musculoskeletal condition. Comparison groups were the following: (1) 100 patients who presented for standard nonoperative musculoskeletal care, and (2) 100 patients who presented for operative evaluation by an orthopedic surgeon and qualified for joint arthroplasty. Intervention: Not applicable. Main Outcome Measures: Primary outcomes were age-adjusted, between-group differences in Patient-Reported Outcomes Measurement Information System (PROMIS) physical and psychological health measures. Secondary outcomes were between-group differences in sociodemographic and medical history characteristics. Results: Patients who enrolled in the intensive lifestyle medicine program were more racially diverse (non-White race: lifestyle cohort 34% vs. comparison cohorts 16%-18%, p ≤.029) and had a higher prevalence of obesity and diabetes than both comparison groups (mean body mass index: lifestyle cohort 37.6 kg/m2 vs. comparison cohorts 29.3-32.0, p <.001; diabetes prevalence: lifestyle cohort 32% vs. comparison cohorts 12%-16%, p ≤.024). Compared to standard nonoperative patients, there were no clear between-group differences in PROMIS physical or psychological health scores. Compared to standard operative evaluation patients, patients in the lifestyle program reported worse anxiety but less pain interference (PROMIS Anxiety: B = 3.8 points [95% confidence interval, 0.1 to 7.4], p =.041; Pain interference: B = −3.6 [−6.0 to −1.2], p =.004). Conclusions: Compared to musculoskeletal patients who sought care through traditional pathways, patients who chose an intensive lifestyle medicine pathway had a higher prevalence of metabolic comorbidities, but there was substantial overlap in patients' physical, psychological, and sociodemographic characteristics.