PurposeTo retrospectively investigate the safety and effectiveness of percutaneous radiofrequency (RF) ablation by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study. Materials and MethodsPatients with lung neoplasm accompanied by ILD who underwent RF ablation between April 2002 and October 2017 at 7 institutions were investigated. Technical success rate and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation. ResultsForty-nine patients with 64 lung neoplasms (mean diameter, 22.6 mm; range, 4–58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RF ablation. Acute exacerbations were seen in 5 sessions (8%, 7% with UIP pattern and 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8–30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever ≥ 38°C after RF ablation were identified by univariate analysis (P = .0012 and P = .02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year. ConclusionsRF ablation appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days after ablation and was associated with a 45% mortality rate.