Background: Next-generation sequencing of cell-free DNA (cfDNA) can assess presence of somatic genomic alterations in patients with cancer without an invasive biopsy. Results may guide therapeutic decision-making. We evaluated use of cfDNA test results for management of breast and lung cancer in a major healthcare system with academic and community-based practices. Methods: Retrospective review of cfDNA tests (Guardant360) ordered for patients with breast or lung cancer at the University of Pittsburgh Medical Center between 8/2014 and 3/2017 was performed. For patients with actionable results (lung: alterations with FDA-approved or NCCN-recommended targeted therapy; breast: ERBB2, ESR1 or PIK3CA alterations), information on clinical care was abstracted. Differences in clinical use of test results were evaluated between academic and community providers. Results: In total, 230 tests were ordered for 218 subjects; 128 by academic and 102 by community providers. Community providers ordered significantly (P < 0.05) more tests for lung cancer patients than academic providers (78% vs. 47%) and their patients were older (mean age: 65.5 vs. 60.3 yrs.). Actionable alterations were identified in 82 subjects (38%; 48 breast, 34 lung). Six were excluded from further analyses because their mutations had been known previously. For 32 (42%) of the remaining 76 subjects, actionable results led to a change in therapy, for the other 44 it did not. Reasons for not changing therapy included: patient died or lost to follow up, palliative care elected, treatment targeted a different molecular finding, targeted therapy recommended but cost prohibitive, and patient currently stable but results could guide therapy at progression. Actionable results significantly more often resulted in a management change for lung cancer than breast cancer (63% vs. 28%). Use of test results differed significantly between academic and community providers (result led to change: 31% vs. 61%) Conclusions: Results of cfDNA tests were used to guide therapy changes, especially for patients with lung cancer. Community practice-based providers appear to act on actionable results more often than academic center-based providers in this health care system.