Selection of the optimal procedure for minimally invasive diagnosis of peripheral pulmonary lesions (PPLs) may be based on clinical factors however selection of diagnostic strategy may also be influenced by cost. Economic analysis of minimally invasive diagnosis of PPL has not been performed previously.Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) with CT-guided percutaneous needle biopsy (CT-PNB). Calculations were based on real costs derived from patient data. Sensitivity analyses, and probabilistic sensitivity analysis, were undertaken to identify the more cost-beneficial approach. for varying input parameter values. Cost-effectiveness calculations were based on estimated disutility, according to the wait-tradeoff technique.For base-case analysis, initial evaluation with CT-PNB was cost-beneficial (CT AU$2,724 v. EBUS-TBLB AU$2,748). The variable which exerted the most influence on cost-benefit outcomes was the cost of managing complications. CT-PNB remained the more cost-effective procedure at base-case parameters, though thresholds were identified during sensitivity analysis where EBUS-TBLB became more cost-effective.The costs of EBUS-TBLB and CT-PNB to evaluate PPL appear to be equivalent, but specific clinicoradiologic factors known to influence procedural outcomes will influence cost-benefit outcomes. Further evaluation of patient preferences and their influence on cost-effectiveness are required.