Shiftwork may be a demanding situation because it raises problems for reconciling work and nonwork activities; as such, this conflict may be mitigated by designing and implementing effective preventative actions at the workplace. There is a paucity of research directly examining the impact of work schedules and preventative measures at work on work-family conflict. Hence, the authors posed the following questions in their study: What is the impact of different work schedules on work-family conflict? Is a preventative culture associated with less work-family conflict? Is work-family conflict associated with specific health and well-being indicators and if so, how does work-family conflict affect well-being as compared with other potential determinants? A subset of 750 nurses ( approximately 10% of total workforce) were randomly selected from a larger sample. Nurses completed the Italian version of the NEXT questionnaire plus newly developed items to create an index on occupational safety and health prevention at work. Data were explored using two data mining techniques, Random Forests and Bayesian Networks, and modeled using hierarchical linear regression models. In all, 664 (88.5% of sample) nurses answered the questionnaire. The authors found that different work schedules had a differential impact on work-family conflict. In addition, effective risk communication between workers and people in charge of safety and health, and participation in preventative activities, quantitative workload, performing tasks not belonging to the nursing profession, and the number of weekends/month spent at work were all strongly associated with work-family conflict. The variable "time schedules" also acted as an effect modifier in the relationship between effective communication and participation in preventative activities and work-family conflict. In addition, quantitative demands played a role as a mediator (30% of total effect) in the relationship between effective communication and participation in preventative activities and work-family conflict. Work-family conflict was significantly associated with burnout, sleep, and presenteeism; its association with burnout was higher than other precursors. Shift schedules that involved night work implied different workload demands, less effective communication, and participation in preventative activities than the other work schedules considered. The presence of a preventative culture directly reduced work-family conflict and indirectly via reduction of work demands. The authors conclude that the development of a preventative culture among irregular and night shiftworkers can be effective in reducing work-family conflict, while positively increasing well-being and job performance.