IMPORTANCE: The prevalence and clinical burden of lymphedema is known to be increasing. Nevertheless, evidence-based comparative effectiveness data regarding lymphedema therapeutic interventions have been poor. OBJECTIVE: To examine the impact of an advanced pneumatic compression device (APCD) on cutaneous and other clinical outcomes and health economic costs in a representative privately insured population of lymphedema patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a deidentified private insurance database from 2007 through 2013, and multivariate regression analysis comparing outcomes for the 12 months before and after APCD purchase, adjusting for baseline patient characteristics. Patients with lymphedema who received an APCD who were commercially insured and Medicare managed care enrollees from a large, national US managed care health insurer. The study population was evaluated as cancer-related and non-cancer-related lymphedema cohorts. INTERVENTION: Receipt of an APCD. MAIN OUTCOMES AND MEASURES: Rates of cellulitis, use of lymphedema-related manual therapy, outpatient hospital visits, and inpatient hospitalizations. Lymphedema-related direct costs were measured for home health care, hospital outpatient care, office visits, emergency department use, and inpatient care. RESULTS: The study sample included 718 patients (374 in the cancer cohort and 344 in the noncancer cohort). In both cohorts, use of an APCD was associated with similar reductions in adjusted rates of cellulitis episodes (from 21.1%to 4.5%in the cancer cohort and 28.8% to 7.3%in the noncancer cohort; P < .001 for both), lymphedema-related manual therapy (from 35.6%to 24.9%in the cancer cohort and 32.3%to 21.2%in the noncancer cohort; P < .001 for both), and outpatient visits (from 58.6%to 41.4%in the cancer cohort and 52.6%to 31.4%in the noncancer cohort; P < .001 for both). Among the cancer cohort, total lymphedemarelated costs per patient, excluding medical equipment costs, were reduced by 37%(from $2597 to $1642, P = .002). The corresponding decline in costs for the noncancer cohort was 36%(from $2937 to $1883, P = .007). CONCLUSIONS AND RELEVANCE: The study found an association between significant reductions in episodes of cellulitis (cancer vs noncancer cohorts) and outpatient care and costs of APCD acquisition within a 1-year time frame in patients with both cancer-related and non-cancer-related lymphedema.