Objective: Fatigue is a common symptom in long-term dialysis patients. This study investigated possible clinical factors which may cause the development of fatigue in patients receiving peritoneal dialysis (PD). We also investigated the relationship between total solute clearance (TSC) and fatigue symptoms in PD patients. Design: A cross-sectional study design was used to compare the clinical characteristics among groups of PD patients classified by different degrees of fatigue. The relationship among dialysis adequacy (including Kt/V<sub>urea</sub> and weekly creatinine clearance; C<sub>cr</sub>), clinical characteristics and fatigue symptoms were also assessed. Setting: The PD unit of a major university teaching hospital in Taipei, Taiwan. Patients: Consecutive patients who had received PD for a minimum duration of 4 months were recruited for participation in the study. Patients were excluded if they had a history of ischemic heart disease, severe heart failure (NYHA function III or IV), malignant neoplasm, active infection, major psychiatric problems, chronic obstructive pulmonary disease, or disturbed consciousness. Finally, a total of 64 patients, 31 of whom were receiving continuous ambulatory peritoneal dialysis and 33 who were receiving continuous cycling-assisted peritoneal dialysis, were enrolled in the study. Methods: Fatigue was evaluated using a specially designed questionnaire that includes fourteen items. Patients were divided into three groups according to their fatigue scores (FS): mild (FS, 0–3), moderate (FS, 4–8), and severe (FS, 9–14) fatigue. The demographic data, dialysis variables, and clinical parameters of patients were compared among these groups. The relationship between fatigue and TSC was also examined. Results: The FS were correlated with serum intact parathyroid hormone (iPTH) level and total cholesterol concentration (p < 0.05). A linear correlation was also noted between serum iPTH level and total cholesterol level. When the patients were divided into an adequate- and an inadequate-dialysis group according to values of TSC, Kt/V<sub>urea</sub> as well as weekly creatinine clearance, a significant correlation was found between weekly C<sub>cr</sub> and FS. Conclusion: This study has demonstrated that dialysis adequacy plays a key role in the development chronic fatigue. In addition, weekly C<sub>cr</sub> was better correlated with fatigue than Kt/V<sub>urea</sub>.