Purpose: Quality of life (QoL) is a well-recognized important measure of therapy outcome, as it reflects what patients perceive as their health condition. The aim of this study was to estimate the QoL in patients on HD and to find the factors that mainly affect it. Patients and Methods: We studied 70 patients on HD (38 male, age 57.86 ± 14.63 years) with the use of kidney disease quality of life short form. Physical health (PH), mental health (MH), kidney disease issues (KDIs), and patient satisfaction (PS) were assessed, as well as Khan comorbidity index, adequacy of dialysis, nutrition, and epidemiologic and laboratory data. Results: PH was significantly correlated with comorbidity (p < 0001), age (p < 0001), duration of HD (p < 0001), serum albumin (Salb) (p < 0005), the existence of a living relative donor (p < 0001), Hb (p < 0.01), and CRP (p < 0.01). MH was significantly correlated to comorbidity (p < 0001), age (p < 0001), duration of HD (p < 0001), Salb (p = 0002), the existence of a living relative donor (p < 0001) and Hb (p < 0.01). KDI score was significantly correlated with comorbidity (p < 0001), age (p < 0001), duration of HD (p < 0001), and Hb (p < 0.05). The acceptance of the method was significantly lower in patients with AVF dysfunction (p < 0005). As much as 44.3% of patients presented inadequate compliance to dietary and fluid restrictions. Conclusion: Frequent QoL assessment in patients on HD is a useful tool for professionals involved in patients' care. Older age, long time on HD, malnutrition, elevated CRP, and comorbid conditions are correlated to lower QoL scores.