BACKGROUND: On March 27, 2020, the city of Philadelphia was given permission by Temple University to convert the Liacouras Center gymnasium to an alternate care site (ACS) to treat low-acuity COVID-19 patients. ACSs, especially those created to specifically care for infectious patients, require a robust infection prevention and control (IPC) program. METHODS: The IPC program was led by a physician and nurse partnership, both of whom had substantial experience developing IPC programs in US and low-resource settings. The IPC program was framed on a previously described conceptual model commonly referred to as the "4S's": Space, Staff, Stuff, and Systems. RESULTS: The gymnasium was transformed into red, yellow, and green infection hazard zones. The IPC team trained 425 staff in critical IPC practices and personal protective equipment standards. Systems to detect staff illness were created and over 3,550 staff health screening surveys completed. DISCUSSION: Use of existing guidance and comprehensive facility and patient management assessments guided the development of the IPC program. Program priorities were to keep staff and patients safe and implement procedures to judiciously use limited resources that affect infection transmission. CONCLUSION: Planning, executing, and evaluating IPC standards and requirements of an ACS during a pandemic requires creative and nimble strategies to adapt, substitute, conserve, reuse, and reallocate IPC space, staff, stuff, and systems.