The objective of this study is to determine risk factors for fatigue among airline pilots, taking into account person-, work-, health-, sleep-, and lifestyle-related characteristics.The study population consisted of 502 pilots who participated in the MORE Energy study. Included risk factors were either measured through an online questionnaire or provided by the company. The outcome of this study, fatigue, was assessed using the Checklist Individual Strength (CIS), and was defined as scoring more than 76 points on this questionnaire. The association of the risk factors with fatigue was determined using univariate and multivariate logistic regression analyses.Of the participating pilots, 29.5 % scored more than 76 points on the CIS and were classified as being fatigued. The fully adjusted regression model showed that person-, work-, health-, and lifestyle-related characteristics were associated with fatigue. Pilots who were aged 31 to 40 (OR 3.36, 95 % CI 1.32-8.53) or 41 to 50 (OR 4.19, 95 % CI 1.40-12.47), an evening type (OR 2.40, 95 % CI 1.38-4.16), scored higher on work-life balance disturbance (OR 1.22, 95 % CI 1.10-1.36), scored higher on need for recovery (OR 1.02, 95 % CI 1.01-1.04), scored lower on general health perception (OR 0.31, 95 % CI 0.20-0.47), were less physically active (OR 0.77, 95 % CI 0.66-0.89), and had a moderate alcohol consumption (OR 3.88, 95 % CI 1.21-12.43), were at higher risk for fatigue.Higher age, being an evening type, disturbance of the work-life balance, more need for recovery, a lower perceived health, less physical activity, and moderate alcohol consumption were shown to be risk factors for fatigue. Further longitudinal research is needed to elucidate the direction of the associations found and to evaluate the effects of possible countermeasures in airline pilots.