Respiratory tract infections (RTIs) and interstitial lung disease (ILD) secondary to interleukin (IL)-12/23 or IL-23 antagonists have been reported in autoimmune diseases.To assess the risk of RTIs and non-infectious ILD with these drugs.We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Risk of RTIs and non-infectious ILD was compared to placebo by Mantel-Haenszel (MH) risk difference (RD). We divided RTIs into upper RTIs (URTI), viral URTIs, and lower RTIs (LRTIs) including infectious pneumonia. Non-infectious ILD included ILD, eosinophilic pneumonia, and pneumonitis.We identified 54 RCTs including 10,907 patients with six IL-12/23 or IL-23 antagonists and 5,175 patients with placebo. These drugs significantly increased the risk of RTIs (MH RD 0.019, 95% confidence interval 0.005-0.033, P = 0.007) which was attributed to URTIs, but not viral URTIs or LRTIs. There was no significant difference in infectious pneumonia and non-infectious ILD between two groups.Due to the rarity of infectious pneumonia and ILD, sensitivity analysis was required.The use of IL-12/23 or IL-23 antagonists for autoimmune diseases increased the risk of URTIs, but not viral URTIs, LRTIs, and non-infectious ILD.