The aim of this study was to assess the effects of physical ergonomic interventions for the prevention of work-related Musculoskeletal Disorders (WMSDs) among office workers. Methods: This was an ergonomic intervention carried out over an 18-month period among medical secretaries (MSs) in three Tunisian teaching hospitals. The first part of this study consisted of screening of WMSDs and a subjective evaluation of workstation. This part also included an ergonomic evaluation of the workstation on screen through open observations and by referring to the International Organization for Standardization (ISO) 9241 covering ergonomics of human-computer interaction. The ergonomic intervention was based on suggestions for improving screen workstations and using poster foldouts. Then, the impact of the ergonomic intervention of workstations on quality of life was assessed. Results: The study population was entirely female. According to the Nordic questionnaire, thirteen secretaries had a single WMSD site. However, more than half of MSs (61.1%) had multi-site WMSDs. The workstation was perceived as unsuitable in 35.6% of cases. The ergonomic study of the workstations revealed the absence of cervical support of chairs in 55.6% of cases. All MSs have benefited from advice to change their behavior and attitude at work. Six months after the intervention, there was a significant improvement of health-related quality of life. Conclusion: This study provides evidence on the effectiveness of a multifaceted ergonomic intervention program designed to reduce WMSDs.