Background: End-stage renal disease and its treatment have a negative impact on the quality of life of patients., Objective: To determine the clinical, dialytic, and laboratory factors associated with poor health-related quality of life in Mexican patients on hemodialysis., Methods: A multicenter, cross-sectional study. The KDQOL-SF36 v1.3 questionnaire was applied to patients with end-stage renal disease on hemodialysis in different regions of Mexico. Patients were classified according to their overall score on the questionnaire: poor health-related quality of life (overall score below the median) or good health-related quality of life (overall score above the median). Clinical, dialytic, and laboratory variables associated with poor health-related quality of life were analyzed using linear correlation and multivariate logistic regression., Results: We included 194 adult patients with a median age of 55 (45-64) years. The diagnosis of poor health-related quality of life was present in 47.4% of patients. A poor correlation was found between the clinical, dialytic, and biochemical parameters and the health-related quality of life score (range of correlations r = -0.4 to 0.2). Serum albumin level showed the highest number of weak, statistically significant correlations. Factors associated with poor health-related quality of life in the multivariate analysis were: time spent on hemodialysis (OR = 1.02; 95% CI; 1.00-1.04; p = 0.02), use of a venous catheter (OR = 3.2; 95% CI: 1.36-7.75; p = 0.01), and serum albumin < 4 g/dl (OR = 3.55; 95% CI: 1.44-8.74; p < 0.01)., Conclusions: Poor health-related quality of life was common in Mexican patients undergoing hemodialysis. No strong correlation was found between the clinical, dialytic, or laboratory factors with health-related quality of life. Factors associated with poor health-related quality of life were: time on hemodialysis, use of a venous catheter, and serum albumin level < 4 g/dl.