Introduction: Serial large volume paracentesis is the most common treatment option for refractory ascites in patients with decompensated cirrhosis. This treatment aims to relieve symptoms and maximize the functionality of the individual’s everyday life, and to generally improve patient’s QoL to any extent, considering the limits imposed by the course of the diseases and patients health status. Purpose of this study is to assess the QoL of patients with decompensated cirrhosis undergoing serial large volume paracentesis. Material and Method: A cohort of 60 patients attending the 2nd Department of Medicine, Medical School of Athens, Hippokration Hospital was recruited. The data were collected with the help of a two-part anonymous self-reported questionnaire consisting of a sheet containing clinical and demographic information and the SF-36 scale. Mean and standard deviation for continuous data and frequencies, and percentages for categorical data were calculated. Non parametric tests such were applied. For the analysis of the data, the statistical package SPPS20 was employed. Results: Out of the total number of participants in the study, 64.41% were men and 35.59% were women. The average age of the respondents was 70.8, with a standard deviation of 10.9 years. More than half (56.14%) were past smokers, 31.58% were current smokers and the remaining 12.28% were non-smokers. The statistical analysis revealed that patients with higher education (p <0.05) reported better scores in QoL on the scales mental health, functionality, and vitality. Women, according to the results of our research, experienced a better QoL on the scale of physical activity than men (p <0.05). Also, those who were not suffering from another disease and were not smokers had a better QoL. Conclusions: Based on the findings of the present study, it appears that factors such as educational level, marital status, age, gender, hospital readmissions can affect the QoL of patients subject to large volume paracentesis. Implementation and evaluation of health education programs aimed at improving the QoL of these patients and their families is of vital importance.