Background: Acne vulgaris is an inflammatory disorder with a profound heterogenous aetio‐pathophysiology. ACE gene I/D polymorphism affects angiotensin‐converting enzyme activities that play a role in inflammation. However, there are no molecular genetic studies investigating the contribution of ACE gene insertion/deletion polymorphism in the genetic background of acne vulgaris. Aims: The aim of this work was to reveal the relation between the ACE gene I/D polymorphism and acne vulgaris development among a sample of patients. Patients and Methods: This study included 100 acne vulgaris patients in addition to 120 matched control subjects. The ACE gene I/D polymorphism was analyzed using polymerase chain reaction (PCR). Results: The distribution of DD, ID genotypes, and D allele showed higher frequency in AV patients than in controls (P < 0.001 for all). Moreover, positive family history and ACEI/D gene polymorphism (DD + ID genotypes) were considered as independent predictors for severe acne grades (P ≤ 0.001 and 0.046, respectively) in multivariate analysis. Conclusions: The current study results suggest that the D allele of the ACE I/D gene polymorphism might confer risk to AV among the studied patients. Moreover, ACE I/D gene polymorphism and positive family history were considered as independent predictors of severe AV.