OBJECTIVES: The high false positive rate associated with low-dose CT documented in the National Lung Screening Trial (NLST) raised major concerns among practitioners because subsequent procedures triggered by the positive findings could be harmful. Our study estimated the complication rate and medical costs associated with these follow-up diagnostic procedures in real-world setting.  METHODS: We identified a nationally representative sample of patients 55-77 years of age who underwent cytology test, biopsy, endoscopy, and/or surgery from MarketScan Commercial Claims & Encounters database and Medicare Supplemental database between 2008 and 2013. The rate of complications was estimated as the excess rate between case patients with the above invasive diagnostic procedures and a matched (by age, sex, and comorbidity) control patients-without these procedures. One-year rates of minor, intermediate, and major complications were calculated after each procedure type and stratified by age groups. Two-part models were adopted to estimate the differences on the complication costs across age groups and each type of procedure.  RESULTS: Our study cohort consisted of 364,567 case and 354,594 control patients. The overall rate of postprocedural complications was 20.2% in young (age <65) patients and 24.1% in older patients. The adjusted medical costs were lowest for minor ($2,561 (young) - $3,245(older)), followed by intermediate ($3,823- $4,845), and major complications ($16,427-$20,819). CONCLUSIONS: For patients undergoing invasive diagnostic procedures for abnormal findings from CT, the complication rates estimated in our study were twice as high as those reported in the NLST, suggesting that the magnitude of harms associated with false positive findings from low-dose CT in community settings is substantially higher than that inferred from the national trial. Developing strategies to reduce harms associated with false positives from low-dose CT scans, especially in practices outside academic medical centers, is critically important for the success of nationwide lung cancer screening program.