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Background: Health‐related quality of life (HRQoL) is significantly and substantially reduced in individuals with peanut allergy due to many factors associated with unanticipated or potentially fatal reactions. Further insight on the impact of peanut oral immunotherapy in managing peanut allergy on HRQoL is needed. The aim of this analysis was to assess effects of peanut (Arachis hypogaea) allergen powder‐dnfp (PTAH), a biologic drug for peanut oral immunotherapy, on HRQoL from three phase 3 and two follow‐on trials of PTAH. Methods: HRQoL assessments from participants aged 4–17 in the PALISADE (ARC003), ARC004 (PALISADE follow‐on), ARTEMIS (ARC010), RAMSES (ARC007), and ARC011 (RAMSES follow‐on) trials were included in this analysis. Responses on the Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) were evaluated by age group and respondent (self or caregiver proxy). Data were analyzed with descriptive statistics and Student t tests. Results: Baseline FAQLQ and FAIM total scores appeared comparable between PTAH‐ and placebo‐treated participants. Self and caregiver proxy‐reported total scores on the FAQLQ for PTAH‐treated participants generally improved at trial exit versus baseline; FAIM total scores improved throughout all trials. The tendency for improvement in FAQLQ total scores from baseline for PTAH appeared larger in self versus caregiver proxy‐reports. Between treatment groups, PTAH was generally favored in the PALISADE and ARTEMIS trials; differences varied in the RAMSES trial based on age and respondent types. Conclusions: PTAH for the management of peanut allergy in children appeared to have a beneficial effect on HRQoL in trials. Improvements were seen despite rigors of trial participation. [ABSTRACT FROM AUTHOR]