The current article examined stoma self-care and health-related quality of life in patients with drainage enterostomy, described clinical and sociodemographic variables and analyzed the relationship between all of them. Trained interviewers collected data using a standardized form that queried sociodemographic and clinical variables. In addition, Self-Care (SC) was measured through a specific questionnaire for Ostomized Patients (CAESPO) and Health-Related Quality of Life (HRQoL) through the Stoma Quality of Life questionnaire (S-QoL), which are not included in the electronic medical record. This was a multicenter, cross sectional study conducted in four hospitals of the province of Castellon (Spain), where 139 participants were studied. As novel findings, it was found that the level of SC of the stoma was high and was positively correlated with health-related quality of life. In relation to SC and sociodemographic variables studied in the research, women, married patients and active workers presented significantly higher scores than the rest. In relation to the clinical variables, we highlight the highest scores of the autonomous patients in the care of their stoma and those who used irrigations regularly. The lowest scores were the patients with complications in their stoma. We can highlight the validity and reliability of the CAESPO scale for biomedical and social research, and the importance of skills related to self-care of ostomy patients for a good level of HRQoL.