ABSTRACT Background Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, frequently severe swelling that negatively impacts patients' quality of life (QoL). In the phase III OASIS‐HAE study (NCT05139810), donidalorsen reduced HAE attack rate, increased disease control, and improved QoL. Here, we report further analysis of donidalorsen's impact on QoL and other patient‐reported outcomes (PROs). Methods This double‐blind, placebo‐controlled study randomized patients with HAE to donidalorsen 80 mg or placebo once every 4 (Q4W) or 8 weeks (Q8W) over 24 weeks. PROs included Angioedema (AE)‐QoL Questionnaire, Angioedema Control Test (AECT), Patient Global Impression of Severity (PGIS), and Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions (WPAI+CIQ). Results Ninety patients received donidalorsen Q4W ( n = 45), donidalorsen Q8W ( n = 23), or placebo ( n = 22). A larger percentage of the donidalorsen Q4W group (88%) achieved clinically meaningful improvement (≥ 6‐point reduction) in AE‐QoL total score vs. placebo (45%). Both donidalorsen groups reported larger least‐squares mean (LSM) changes from baseline to week 24 vs. placebo in AE‐QoL functioning (difference: Q4W, −24.5; Q8W, −16.1), fears/shame (Q4W, −23.9; Q8W, −20.1), and nutrition (Q4W, −15.7; Q8W, −10.7) domains. Donidalorsen improved AECT scores vs. placebo (difference: Q4W, 6.0; Q8W, 4.1). A greater proportion of the donidalorsen Q4W group reported decreased disease severity vs. the placebo group (PGIS; 82% vs. 44%). Donidalorsen Q4W showed benefits vs. placebo in the presenteeism, overall work/school impairment, and activity impairment domains of the WPAI+CIQ. Conclusions Donidalorsen significantly improved QoL and other PROs vs. placebo in patients with HAE.