Background: OCD causes impairment in different areas of the patients' quality of life (QoL), such as sociability, family relationships, and occupational performance. The literature has emphasized the relevance of assessing QoL as a critical outcome in mental health studies. Aims: The aim of this study was to investigate sociodemographic and clinical predictors of QoL, including treatment response, in a large sample of OCD subjects. Procedures: 575 adult OCD outpatients were interviewed as part of the Brazilian OCD Consortium (CTOC). A smaller number of subjects (N = 143) participated on a clinical trial conducted by one of the CTOC sites. Results: OCD patients were more impaired in their QoL when compared to the Brazilian normative data. Obsessive-compulsive symptoms (OCS) severity had significant correlations with all Medical Outcome Short-Form questionnaire (SF-36) domains. Different OCS dimensions had specific correlations with each SF-36 domain. OCS, depression and anxiety severity significantly increased the impairment risk for the SF-36 domains. Suicidality increased the relative risks for impairment in the Role-Functioning and the Vitality domains by 51% and 17%, respectively. There was a significant improvement in some SF-36 dimensions after treatment. Conclusions: QoL domains are highly compromised in OCD patients. Each SF-36 domain had distinct associations with sociodemographic and clinical variables, including OCS dimensions, suicidality and treatment response. These findings emphasize the OCD heterogeneity and the need for including QoL assessment in clinical practice and research studies.