Background: Sample adequacy for immediate molecular testing is paramount in lung cancer. To date, several endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) sampling setups have been evaluated, however, the utilization of high-pressure suction (HPS) has not yet been reported. The aim of this study was to evaluate the utilization of HPS onto the needle and its effect on sample volume and adequacy for molecular testing in patients with suspected lung cancer.Methods: We retrospectively analyzed 128 consecutive EBUS-TBNA performed for suspected lung cancer. This was confirmed in 109 patients. Other diagnoses confirmed in 12, and 7 referred for surgery. Sixty-three patients (89 targets) had HPS (May to September 2020), and compared with 46 (72 targets) who had standard vacuum syringe suction (October 2019 to March 2020). Several parameters and outcomes evaluated, such as number of needle passes, needle strokes, needle size, target size, positron emission tomography avidity, procedure time, blood content score, sample volume, adequacy for molecular testing, as well as baseline patient characteristics and complication rate.Results: There was no difference between the 2 groups in all baseline parameters and characteristics. In multivariable analysis, HPS was associated with significantly higher sample volume (11.2 vs. 9.1 mm 3 , P = 0.036) and less additional procedures to achieve full molecular profiling (2/ 52 vs. 7/40, P = 0.042), in necrotic targets of non−small cell lung cancer. Diagnostic yields were comparable.Conclusion: HPS appears to be simple, no-cost, and safe, promising higher sample volume compared with vacuum syringe suction, and also appears to be associated with higher success of full molecular testing with less additional procedures, in non−small cell lung cancer necrotic targets.