BACKGROUND: Current evidence linking long-term exposure to fine particulate matter (PM2.5) exposure and mortality is primarily based on persons that live in the same residence, city and/or country throughout the study, with few residential moves or relocations. We propose a novel method to quantify the health impacts of PM2.5 for United States (US) diplomats who regularly relocate to international cities with different PM2.5 levels. METHODS: Life table methods were applied at an individual-level to US mortality statistics using the World Health Organization's database of city-specific PM2.5 annual mean concentrations. Global Burden of Disease concentration-response (C-R) functions were used to estimate cause-specific mortality and days of life lost (DLL) for a range of illustrative 20-year diplomatic assignments for three age groups. Time lags between exposure and exposure-related mortality risks were applied. Sensitivity analysis of baseline mortality, exposure level, C-R functions and lags was conducted. The effect of mitigation measures, including the addition of air purifiers, was examined. RESULTS: DLL due to PM2.5 exposure for a standard 20-year assignment ranged from 0.3 days for diplomats' children to 84.1 days for older diplomats. DLL decreased when assignments in high PM2.5 cities were followed by assignments in low PM2.5 cities: 162.5 DLL when spending 20 years in high PM2.5 cities compared to 62.6 DLL when spending one of every four years (5 years total) in a high PM2.5 city for older male diplomats. Use of air purifiers and improved home tightness in polluted cities may halve DLL due to PM2.5 exposure. The results were highly sensitive to lag assumptions: DLL increased by 68% without inception lags and decreased by 59% without cessation lags for older male diplomats. CONCLUSION: We developed a model to quantify health impacts of changing PM2.5 exposure for a population with frequent relocations. Our model suggests that alternating assignments in high and low PM2.5 cities may help reduce PM2.5-related mortality burdens. Adding exposure mitigation at home may help reduce PM2.5 related mortality. Further research on outcome-specific lag structures is needed to improve the model.