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Objective The goal of this study was to evaluate and compare lower-leg muscle fatigue, edema, and discomfort induced by the prolonged standing of security guards wearing regular socks and those wearing 15–20 or 20–30 mmHg compression stockings as intervention. Background Compression stockings are sometimes used by individuals standing all day at work. However, quantitative evidence showing their potential benefits for lower-leg health issues in healthy individuals during real working conditions is lacking. Method Forty male security employees participated in the study. All were randomly assigned to the control or one of the two intervention groups (I15–20 or I20–30). Lower-leg muscle twitch force, volume, and discomfort ratings were measured before and after their regular 12-hr standing work shift. Results Significant evidence of lower-leg long-lasting muscle fatigue, edema, and discomfort was observed after standing work for guards wearing regular socks. However, no significant changes were found for guards wearing either compression stockings. Conclusion In healthy individuals, compression stockings seem to attenuate efficiently the tested outcomes in the lower leg resulting from prolonged standing. Application Occupational activities requiring prolonged standing may benefit from 15–20 or 20–30 mmHg compression stockings. As similar benefits were observed for both levels of compression, the lower level may be sufficient.