Patients with hypertension (HTN) face an increased risk of complications and mortality from influenza; a risk that may be modified by influenza vaccination. There is limited evidence on the effectiveness of high-dose (HD-IIV) compared with standard-dose (SD-IIV) inactivated influenza vaccines in hypertensive individuals. This study, a post hoc analysis of DANFLU-1, a pragmatic, and open-label, individually randomized trial of HD-IIV vs. SD-IIV conducted during the 2021-2022 influenza season among participants aged 65-79 years. Prespecified outcomes in DANFLU-1 included hospitalization for influenza or pneumonia, cardiovascular, cardiorespiratory, and respiratory hospitalizations, all-cause hospitalization, and all-cause mortality. Outcomes were analyzed as both time-to-first and recurrent events. DANFLU-1 randomized 12 477 participants randomized to HD-IIV or SD-IIV, of these 6469 (51.9%) had a history of HTN. HD-IIV was associated with lower hazards for hospitalizations for pneumonia or influenza, respiratory disease, and all-cause mortality compared with SD-IIV and these associations were consistent regardless of HTN status (pinteraction = 0.09, = 0.09, and = 0.59, respectively). HD-IIV was associated with lower incidence rates of recurrent hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with SD-IIV, irrespective of HTN status (pinteraction = 0.09 and = 0.75, respectively). There was evidence of potential effect modification of HD-IIV vs. SD-IIV in relation to recurrent respiratory hospitalizations, where the relative effect may be greater among those without vs. with HTN (pinteraction = 0.04). In conclusion, this post hoc analysis of a large-scale pragmatic trial, HD-IIV was associated with lower risk of clinical outcomes, including hospitalizations for pneumonia or influenza, all-cause mortality, and all-cause hospitalizations irrespective of the presence of HTN. Trial Registration: ClinicalTrials.gov identifier: NCT05048589.