Visual fatigue and discomfort are very common complaints for video display operators (VDTs). The aim of our study was to study work-related visual symptoms in relation to refractive disorders and psychosocial factors in 3054 public employees by way of follow-ups for 10 years with periodic medical examinations with eye evaluation in the period 2000–2009. Factors related to visual fatigue were evaluated in the follow-up using generalized equation estimation. Visual fatigue was very common in VDT operators (64.03%). During the follow-up, no relationship between visual fatigue and age, sex, seniority of work, visual acuity and refractory disorders was found. Visual fatigue was significantly associated with anxiety perception in a dose-related matter (odds ratio (OR) 7.40, confidence interval (CI) 95% 1.77–31.3), psychosocial factors (OR 1.03, CI 95% 1.01–1.07), use of lenses (OR 1.34, CI 95% 1.09–1.64) and time of VDT usage (OR 1.27, CI 95% 1.04–1.53). This study confirmed that visual fatigue is common in VDT users and is related to anxiety perception, time of VDT usage, use of lenses and stress. No relationship was found between visual fatigue and refractory disorders or visual acuity.