Aim: To assess the theoretical impact of workplace-based primary interventions designed to reduce exposure to personal and/or work-related risk factors for LDS. Methods: Cases of LDS were assessed using hospital discharge records for persons aged 20–64 in 2007–8 in the French Pays de la Loire region. We estimated the number of work-related cases of LDS (WR-LDS) in high-risk industry sectors. Three theoretical scenarios of workplace-based primary prevention for sectors at risk have been simulated: a mono-component work-centered intervention reducing the incidence of WR-LDS by 10% (10%-WI), and two multicomponent global interventions reducing the incidence of all cases of LDS by 5% (5%-GI) and 10% (10%-GI) by targeting personal and occupational risk factors. Results: Four industry sectors were at high risk of LDS in the region, amounting to 435 [351–532] LDS cases, of which 152 [68–253] were WR-LDS: construction and information & communication for men; wholesale & retail trade and accommodation & food service activities for women. AFE was limited for each industry sector, 30%, 50%, 33% and 55%, respectively. The 10%-WI, 5%-GI and 10%-GI scenarios hypothetically prevented 15 [7–25], 22 [18–27] and 44 [35–53] LDS cases among sectors at risk, respectively. Discussion: Prevention scenarios combining actions on personal and occupational risk factors would be the most effective, compared to prevention focused only on occupational risk factors. This suggests that, to reduce the incidence of LDS, implementing actions of promotion of health at work would be necessary in addition of actions on occupational risks.