Musculoskeletal disorders (MSDs) present a major occupational health challenge, especially among office workers. Objective: To evaluate the effectiveness of a workplace intervention program for managing MSDs and measure its impact on presenteeism/absenteeism and health status. Methods: This semi-experimental study was conducted between May 2019 and October 2022 in Greece and involved 247 office workers randomly assigned to early and late intervention groups. The intervention included a seminar on ergonomics and proper workstation practices with a demonstration of exercises. Data were collected by the SF-36, the Standardised Nordic, and the Work Productivity and Activity Impairment Questionnaires. Results: In the early intervention group (n = 143), presenteeism significantly decreased (p = 0.045), from a mean value of 0.11 to 0.07, but not absenteeism. Significant improvements were observed in physical (p = 0.007) and mental health (p = 0.012). Reductions in pain were recorded for the neck (p = 0.032), shoulders (p = 0.015), wrists (p = 0.014), upper back, lower back, hips, and knees (p = 0.044 for each). In the late intervention group (n=104), there were no significant changes in absenteeism or presenteeism. Mental health improved significantly (p = 0.008), and reductions in pain were noted for the neck (p = 0.001), wrist (p = 0.0005), and upper back (p = 0.001). Conclusions: This workplace intervention program proved effective both in reducing pain in various body areas and reducing presenteeism, and improved physical and mental health were observed in the intervention groups while absenteeism remained unchanged.