Aims and objectives. The main goal of nursing care should be to increase health-related quality of life as well as improve the medical status of patients with chronic disease. For this reason, this study aims to evaluate and compare the health-related quality of life of patients with diabetes mellitus, hypertension and obesity in Gaziantep, a south-eastern city in Turkey. Background. Diabetes mellitus, hypertension and obesity are the most decisive factors in terms of adversely affecting health-related quality of life. Design. A cross-sectional, descriptive design was used. Method. In this study, the research population included a total of 1601 diabetes mellitus, hypertension and obesity patients. To evaluate health-related quality of life of patients, Short Form-36 (SF-36) was used. Student's t-test, one-way anova and chi-square analyses were used for comparisons between groups. Results. In total, 18 center dot 1% of patients had combined obesity, hypertension and diabetes mellitus; 16 center dot 1% had hypertension and diabetes mellitus. Approximately 16 center dot 1% had only hypertension; 15 center dot 4% had obesity and hypertension; 13 center dot 3% had diabetes mellitus; 12 center dot 7% had obesity and diabetes mellitus; and 8 center dot 4% had obesity. The health-related quality of life physical component mean scores of patients with combined obesity and hypertension were lower than that of the other groups (p < 0 center dot 05). Health-related quality of life physical component mean scores were determined as 34 center dot 5 (SD 0 center dot 4), and mental component mean scores were determined as 43 center dot 9 (SD 4 center dot 4). Health-related quality of life physical component mean scores of moderately active patients were higher, while older age and lower educational and income levels had a negative effect on health-related quality of life (p < 0 center dot 05). Conclusion. Diabetes, hypertension and obesity decrease patient health-related quality of life while physical activity increases it. The coexistence of obesity and hypertension, in particular, has a more negative effect on health-related quality of life. Relevance to clinical practice. Patients with hypertension, obesity and diabetes mellitus need professional support from nurse. Frequent health-related quality of life evaluation and support is required for chronic patients, especially for those who are older, have lower educational and income levels and those with more than one chronic disease.