BACKGROUND Fatigue among thyroid cancer survivors is an important issue that needs to be appreciated and managed appropriately. Although several studies have reported potential factors that might be related to postoperative fatigue, the associations have yet to be inconclusive. The purpose of the present study was to estimate the prevalence of clinical fatigue in patients with papillary thyroid carcinoma and to reveal predictive factors, including their quality of life. METHODS A cross-sectional survey was conducted on patients with papillary thyroid carcinoma. Patients who underwent non-curative surgery, or those with recurrent or metastatic PTC, or those with other malignancies were excluded. The primary outcome was fatigue measured by the Cancer Fatigue Scale (CFS), and the secondary outcome was quality of life (QoL) quantified using the SF-36 v2. The following explanatory variables were collected; gender, age, employment status, marital status, co-morbidities, time since initial surgery, types of surgery, replacement of thyroid hormone, use of radioactive iodine, and the level of thyrotropin. The prevalence of clinical fatigue was estimated with the cut-off value of 18/19 of the CFS score. Correlations between the CFS score and the explanatory variables were examined using uni-variable analyses as well as multi-variable analysis. RESULTS Three hundred twenty-one patients participated in the survey. Of them, 258 respondents (80%) were female. The median age was 58 years, and the median time from initial surgery was 6.4 years. The mean and the standard deviation of the CFS score were 17.9 and 9.3, respectively (range: 0-48). The prevalence of clinical fatigue was 42% [95%CI: 36-47%]. Among the variables explored, having a job and scores of the mental component summary, the physical component summary, and the role/social component summary of the SF-36 were inversely associated with the CFS score in both uni- and multivariable analyses. CONCLUSION Postoperative fatigue was common in thyroid cancer survivors. Patients with a job and better QoL, in particular, those with good mental health, maybe at low-risk of developing the burden.