Infection Prevention and Control (IPC) practices have been established in home health care. Adherence to IPC practices has been suboptimal with limited available evidence. The study aim was to examine the impact of individual, home environment, and organizational factors on IPC practices using human factors model. Three hundred and fifty-three nurses were surveyed across two large home care agencies to examine the relationship between IPC adherence and individual, home environment, and organizational factors. Nurses reported multiple barriers to IPC practices in patients' homes (mean = 4.34, standard deviation = 2.53). Frequent barriers included clutter (reported by 74.5% of nurses) and a dirty environment (70.3%). Nurses also reported limited availability of some IPC supplies (mean = 7.76, standard deviation = 2.44), including personal protective equipment. Home environment factors were significant barriers, and availability of IPC supplies were significant enablers of IPC adherence. Agency-provided training and decision-making resources were not significant factors for IPC adherence in the presence of home environment barriers and IPC supplies. This study findings suggest that IPC adherence strategies point to addressing barriers in the home environment and increasing availability of IPC supplies. The relationship between the patient's home environment, organizational factors, and IPC practices among home health care nurses warrants further study.