Purpose: It is unclear how and to what extent various infection prevention and control (IPC) policies affect the spread of an epidemic during work resumption. In order to assess the impact of IPC policies, this research addresses the results of a policy simulation in Shanghai, China, which estimates the transmission dynamics of COVID-19 under various IPC policies and offers evidence-based outcomes of work resumption policies for the world. Materials and Methods: This simulation research is based on a system dynamics (SD) model that integrates IPC work resumption policies implemented in Shanghai into the classical susceptible-exposed-infected-removed (SEIR) epidemiological model. Input data were obtained from official websites, the Baidu migration index and published literature. The SD model was validated by comparing results with real-world data. Results: The simulations show that a non-quarantined and non-staged approach to work resumption (Policy 1) would bring a small secondary outbreak of COVID-19. The quarantined but non-staged approach (Policy 2) and the non-quarantined but staged approach (Policy 3) would not bring a secondary outbreak of COVID-19. However, they both would generate more newly confirmed cases than the staged and quarantined approach (Policy 4). Moreover, the 14-day quarantine policy alone appears to be more effective in reducing transmission risk than the staged work resumption policy alone. The combined staged and quarantined IPC policy led to the fewest confirmed cases caused by work resumption in Shanghai, and the spread of COVID-19 stopped (ie, the number of newly confirmed cases reduced to zero) at the earliest date. Conclusion: Conservative IPC policies can prevent a second outbreak of COVID-19 during work resumption. The dynamic systems model designed in this study can serve as a tool to test various IPC work resumption policies, facilitating decision-making in responses to combating the COVID-19 pandemic. © 2020 Zhao et al.