© 2021 the International Society of DermatologyBackground: Acne vulgaris is a chronic inflammatory skin disease that affects the pilosebaceous unit. Although it is considered to be a skin-limited disease, different clinical studies have recently been published in which the disease is accompanied by systemic symptoms. In this study, systemic comorbidities accompanying acne vulgaris and the relationship between existing comorbidities and disease severity are investigated. Methods: This prospective multicenter study was conducted by the Turkish Society of Dermatology Acne Study Group. Twelve dermatology clinics and 14 clinicians throughout Turkey participated in the study. A structured physician-administered questionnaire was used to collect patient demographics, clinical findings, and lifestyle data. Physicians recorded each participant’s medical history, including current and past comorbidities, duration of any comorbidity, smoking, and drinking. Body mass index (BMI) was calculated. Results: There were 3022 patients in the adolescent acne group and 897 in the control group. The incidence of nonmigraine headache in adolescents with acne was significantly higher than in the nonacne group (P = 0.019). There were 680 patients in the postadolescent acne group and 545 in the control group. In the postadolescent group, incidence of metabolic disease was lower than the control group (P = 0.003). In the postadolescent group, premenstrual syndrome (P < 0.001) and PCOS (P = 0.007) were more common than the control group. Conclusions: In this study, we observed that acne vulgaris does not cause systemic comorbidities. There is also a need for new studies involving a large number of patients to illuminate systemic diseases accompanying acne vulgaris.