Psycho-physical well-being of video display terminal (VDT) workers is often neglected. The aim of this study is to evaluate, through the comparison of controlled studies published in scientific literature, the psycho-physical well-being of VDT workers and, in particular way, the phenomena of strain and mental fatigue with their neuro-physiological, behavioural and subjective components. Seven-hundreds articles have been found from which we have selected twenty-one articles on the basis of the following inclusion criteria: controlled studies and evaluation of variables about mental fatigue; finally, only fifteen articles were utilized in the analysis due to the variability of data needed in the computation of effect size. For continuous variables we have performed two different types of elaboration methods; in case of variables showing no significant heterogeneity among studies, we have used the Weighted Mean Difference method, according to the Fixed Effect Model, while for variables showing significant heterogeneity among studies, we have used the Standardized Mean Difference method according to the Random Effects Model. Categorical variables have been analyzed trough the calculation of Odds Ratio according to the Fixed Effect Model or to the Random Effects Model respectively in case of heterogeneity's absence or presence among studies. Variables obtained by the studies were classified in four groups: biological assessment, strain assessment, subjective well-being assessment, and psycho-somatic symptoms. Statistically significant outcomes have been found for urinary adrenalin, sleep disturbances and for all the evaluated categorical parameters except headache. These outcomes allow for the following observations: 1) psycho-physical well-being of VDT workers, and especially mental fatigue, remain an object of uncertain identification and they are often neglected by Occupational Health doctors even though their evaluation is required by the Italian legislation (D.Lgs 626/94); 2) even though there is a huge interest on the argument, the amount of controlled studies on VDT workers is still insufficient. Furthermore, studies are often weak in power heterogeneous and discordant on potential problematic issues and consequently there is a difficulty in both the reproduction and overlapping of the studies; 3) Occupational Health doctor should be more careful toward this specific argument and, in his clinical practice, he should use only evidence-based parameters with high level of reproduction suggested by studied which can be considered homogeneous and overlapping for case studies and control groups. This meta-analysis suggests which evaluations to use as statistically significant parameters for the health protection of VDT workers.