IMPORTANCE The use of acellular dermal matrix (ADM) in implant-based breast reconstructions (IBBRs) is established practice. Existing evidence validating ADMs proposed advantages, including improved cosmetics and more single-stage IBBRs, is lacking. OBJECTIVE To evaluate whether IBBR with ADM results in fewer reoperations and increased healthrelated quality of life (HRQoL) compared with conventional IBBR without ADM. DESIGN, SETTING, AND PARTICIPANTS This was an open-label, multicenter, randomized clinical trial of women with primary breast cancer who planned for mastectomy and immediate IBBR, with a 2-year follow-up for all participants. Participants were enrolled at 5 breast cancer units in Sweden and the United Kingdom between 2014 and May 2017. Exclusion criteria included previous radiotherapy and neo-adjuvant chemotherapy. Data were analyzed until August 2017. INTERVENTIONS Participants were allocated to immediate IBBR with or without ADM. MAIN OUTCOMES AND MEASURES The primary trial end point was number of reoperations at 2 years. HRQoL, a secondary end point, was measured as patient-reported outcome measures using 3 instruments from the European Organization for Research and Treatment of Cancer Quality of life Questionnaire.