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The aim of this study is to document the relationship between anger dimensions (state, trait, expression, and control) and quality of life (QoL) in patients co-infected with HIV and hepatitis C virus (HCV).This is a cross-sectional study nested in the ANRS CO13-HEPAVIH French national cohort. Anger and QoL were assessed using self-administered questionnaires in 536 HIV–HCV-co-infected patients. Correlations between anger scores (STAXI-2 scale) and QoL scores (WHOQOL-HIV BREF scale) were assessed using Spearman’s coefficients. Multiple linear regression models were then used to test the relationship between the different dimensions of anger and QoL after adjustment for statistically significant psychosocial, sociobehavioral, and clinical characteristics.Patients with excessive alcohol use or history of injecting drug use had higher levels of anger. All dimensions of anger were significantly correlated with impaired QoL for all six dimensions of the WHOQOL-HIV BREF scale. Greater internal experience of anger and impaired anger control were confirmed as independent correlates of impaired QoL related to psychological health, social relationships, and patients’ beliefs after adjustment for depressive symptoms, functional impact of fatigue, socioeconomic status, and HIV-related characteristics.Anger issues need close monitoring in HIV–HCV-co-infected patients, especially in patients with addictive behaviors. Screening for problems in anger management and implementing individualized psychotherapeutic strategies may help improve QoL in this population.