BACKGROUND: The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. METHODS: Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (beta) and multiple adjusted odds ratios (OR) were calculated as measures of association. RESULTS: WLC was found to be quite strongly associated with MSD (beta=.21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r=.44). A significant and relevant association still remained (beta=.10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR=3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR=1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. CONCLUSION: Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study.