Background <p>Acne vulgaris (acne) is a common dermatological condition that can profoundly affect psychosocial well-being. Health-related quality of life (HRQoL) is an important outcome measure to assess the burden of acne in research and clinical practice.</p> Objective <p>This systematic review aimed to identify, critically appraise, and synthesize current evidence on the effects of acne on HRQoL and other psychosocial outcomes.</p> Methods <p>Structured searches of PubMed and Web of Science were conducted to identify studies measuring any HRQoL or psychosocial outcome in patients with acne vulgaris (all ages). Eligible studies were those that included ≥ 50 patients with acne, measured HRQoL or psychosocial outcomes as primary endpoints, were conducted in Europe and North America, and were published in English from 1 January 2014 to 30 April 2024. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.</p> Results <p>In total, 101 studies were deemed eligible for inclusion. They varied widely in terms of study design, population, outcomes, and quality, but overall demonstrated the adverse impacts of acne on HRQoL, mental health outcomes, and the lived experiences of people with acne. Despite their heterogeneity, studies frequently found that acne predominantly affected the emotional and psychological domains of HRQoL, and was particularly burdensome to adults, females, and those with more severe acne.</p> Conclusions <p>This review collated the spectrum of impacts that acne vulgaris can impose on psychosocial well-being, and highlighted the need for consensus outcome measures to streamline future research and improve clinical practice.</p> PROSPERO Registration <p>CRD42024539174.</p>