This study investigates the frequency and nature of adverse events associated with the use of type 2 biologics (dupilumab and mepolizumab) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). A single-institution retrospective chart review was conducted, including 87 patients on dupilumab and 51 on mepolizumab. The study found that 45% of dupilumab users and 20% of mepolizumab users experienced adverse events, which differed from phase 3 trial data. The adjusted odds ratio for adverse event rates between the two groups was 3.8 (95% CI, 1.5–10.5). Common adverse events for dupilumab included arthralgia, rash, and conjunctivitis or xerophthalmia, while those for mepolizumab were headache and fatigue. Seven dupilumab and three mepolizumab patients discontinued therapy due to adverse events. The average treatment duration was 22.5 months for mepolizumab and 15.9 months for dupilumab. The study concludes that dupilumab and mepolizumab have distinct adverse event profiles, and these findings can inform clinicians' decisions regarding the use of type 2 biologics in CRSwNP patients.This study investigates the frequency and nature of adverse events associated with the use of type 2 biologics (dupilumab and mepolizumab) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). A single-institution retrospective chart review was conducted, including 87 patients on dupilumab and 51 on mepolizumab. The study found that 45% of dupilumab users and 20% of mepolizumab users experienced adverse events, which differed from phase 3 trial data. The adjusted odds ratio for adverse event rates between the two groups was 3.8 (95% CI, 1.5–10.5). Common adverse events for dupilumab included arthralgia, rash, and conjunctivitis or xerophthalmia, while those for mepolizumab were headache and fatigue. Seven dupilumab and three mepolizumab patients discontinued therapy due to adverse events. The average treatment duration was 22.5 months for mepolizumab and 15.9 months for dupilumab. The study concludes that dupilumab and mepolizumab have distinct adverse event profiles, and these findings can inform clinicians' decisions regarding the use of type 2 biologics in CRSwNP patients.