Abstract Background and Aims Gastrointestinal (GI) symptoms are common among patients with chronic renal failure, especially in those treated with maintenance hemodialysis (HD), and may adversely affect patients'' quality of life. A variety of GI symptoms has been reported, but previous studies present conflicting results regarding their association with age, sex, comorbidities, concomitant medications and dialysis modality. This study aimed to assess the prevalence and severity of GI symptoms in the maintenance HD population and explore possible associated factors. Method A total of 188 stable patients (55.3% male, 53.7% ≥65 years of age, age range 24–85, 30.9% with diabetes, 19.9% smokers) from three HD centres were enrolled in this observational cross-sectional study. Gastrointestinal symptoms were assessed by the self-administered Gastrointestinal Symptoms Rating Scale (GSRS). The scale includes 15 items graded by a 7-point Likert scale that can be grouped into five dimensions: abdominal pain syndrome, reflux syndrome, indigestion syndrome, diarrhoea syndrome, and constipation syndrome. A dimension score is calculated as the mean value of the items belonging to the specific syndrome, and the final score is the mean of dimension scores. Standard blood analyses, Kt/V, body mass index (BMI) and malnutrition-inflammation score (MIS) were determined in all patients. Other relevant demographic and clinical data were obtained from the patient's medical records. The results were analyzed with SPSS software, version 22 (IBM Corporation, New York, USA). Results The average BMI was 25.04±4.29. Half of the patients (50.3%) were overweight, 45.3% had normal weight, and 4.3% were underweight. The average MIS was 5.64±2.87. The average number of symptoms per patient was 4.01±3.20 (range 0 – 15). At least one GI symptom was reported by 84.6% of patients (33.0% reported 1 – 3 symptoms, and 49.5% reported 4 or more symptoms). The mean GSRS scores for eating dysfunctions were 1.59±1.08 for reflux, 1.74±0.98 for abdominal pain, 1.75±1.14 for constipation, 1.94±1.01 for indigestion, and 1.38±0.90 for diarrhoea. Total GSRS was 1.70±0.61. Elderly patients had a significantly lower overall number of GI symptoms (3.49±2.83 vs 4.57±3.51; p = 0.023), lower abdominal pain score (1.60±0.96 vs 1.91±1.09; p = 0.031), and indigestion score (1.74±0.85 vs 2.18±1.15; p = 0.005), but higher constipation (1.94±1.27 vs 1.54±0.96;p = 0.017) score than individuals under 65 years of age. Patients smoking cigarettes and those longer on HD had a significantly higher overall number of GI symptoms (3.44±0.56 vs 3.10±0.25; p = 0.035 and 3.78±2.99 vs 2.46±2.23; p = 0.016 respectively). Average abdominal pain score was significantly higher in non-diabetic (1.87±1.04 vs 1.44±0.75; p = 0.002) and underweight (2.62±1.51 vs 1.71±0.94 vs 1.65±0.90; p = 0.023) compared to diabetic, normal weight and overweight patients respectively. Patients taking ASA or NSAIDs had significantly higher total GSRS scores (1.84±0.72 vs 1.60±0.50; p = 0.016 and 1.88±0.64 vs 1.65±0.59; p = 0.044 respectively). Sex, dialysis adequacy and malnutrition-inflammation status were not significantly related to any of the GSRS dimensions. Conclusion The present study demonstrates a high prevalence of GI symptoms in maintenance HD patients and identifies age, cigarette smoking, diabetes, dialysis vintage, and certain medications as important elements to consider when addressing specific groups of GI symptoms in this population.