BACKGROUND: Obesity is a known risk factor and aggravator of musculoskeletal (MSK) conditions. The rising prevalence of obesity calls for scalable solutions to address MSK conditions in this population, given their complex clinical profile and barriers to accessing care. PURPOSE: To evaluate the engagement and clinical outcomes of a fully remote digital care program in patients with MSK conditions, focusing on those with and without comorbid obesity. PATIENTS AND METHODS: A post-hoc analysis of a prospective, longitudinal, single-arm observational home-based study conducted between August, 2023, and August, 2024. Adults suffering from chronic MSK pain were categorized according to their body mass index (BMI) into non-obesity, obesity and severe obesity. Outcomes included completion rates, engagement, satisfaction, pain (minimal clinically important change: 30%), impairment in daily activities, and patient global impression of change (PGIC). Depending on the clinical outcomes, latent basis growth analysis and logistic regression were used. RESULTS: Completion rates were high across all groups (77.5-85.6%), although slightly lower in the obesity groups. Fairly similar engagement was observed with both exercise sessions and the educational content (1.9-2.2 exercise sessions per week; 8.10-9.31 educational content videos watched). Obesity groups interacted more with the physical therapists than the non-obesity group (severe obesity: 24.6 (SD 10.1); obesity: 23.2 (SD 10.46) vs non-obesity: 22.4 (SD 9.8), P < 0.001). Despite higher baseline risk and clinical impairment in the obesity groups, all groups showed significant pain reductions, with pain responder rates ranging from 56.6 to 63.6%, slightly lower in the severe obesity group. Improvements in daily activities were significant across groups, alongside a positive PGIC (50.4-53.6%). Satisfaction was very high (>9/10) in all BMI groups. CONCLUSION: Despite worse baseline clinical presentations, obesity groups achieved high completion rates, engagement, and significant clinical improvements comparable to the non-obesity group, highlighting the potential of a digital program for this population.