A blood-based integrated classifier (IC) has been clinically validated to improve accuracy in assessing probability of cancer risk (pCA) for pulmonary nodules (PN). This study evaluated the clinical utility of this biomarker for its ability to reduce invasive procedures in patients with pre-test pCA ≤ 50%. This was a propensity score matching (PSM) cohort study comparing patients in the ORACLE prospective, multicenter, observational registry to control patients treated with usual care. This study enrolled patients meeting the intended use criteria for IC testing: pCA ≤ 50%, age ≥40 years, nodule diameter 8–30 mm, and no history of lung cancer and/or active cancer (except for non-melanomatous skin cancer) within 5 years. The primary aim of this study was to evaluate invasive procedure use on benign PNs of registry patients as compared to control patients. A total of 280 IC tested, and 278 control patients met eligibility and analysis criteria and 197 were in each group after PSM (IC and control groups). Patients in the IC group were 74% less likely to undergo an invasive procedure as compared to the control group (absolute difference 14%, p <0.001) indicating that for every 7 patients tested, one unnecessary invasive procedure was avoided. Invasive procedure reduction corresponded to a reduction in risk classification, with 71 patients (36%) in the IC group classified as low risk (pCA < 5%). The proportion of IC group patients with malignant PNs sent to surveillance were not statistically different than the control group, 7.5% vs 3.5% for the IC vs. control groups, respectively (absolute difference 3.91%, p 0.075). The IC for patients with a newly discovered PN has demonstrated valuable clinical utility in a real-world setting. Use of this biomarker can change physicians’ practice and reduce invasive procedures in patients with benign pulmonary nodules.Trial registration: Clinical trial registration: ClinicalTrials.govNCT03766958.