Background Care institutions are recognised to be a high-risk setting for the emergence and spread of infections and antimicrobial-resistant organisms, which stresses the importance of infection prevention and control (IPC). Accurate implementation is crucial for optimal IPC practice. Despite the wide promotion of IPC and research thereof in the hospital and nursing home setting, similar efforts are lacking in disability care settings. Therefore, this study aimed to assess perceived barriers and facilitators to IPC among professionals working at residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDD), as well as to identify professional-reported recommendations to improve IPC. Methods This qualitative study involved semi-structured interviews (before COVID-19) with twelve professionals from five Dutch RCFs for people with IDD. An integrated theoretical approach was used to inform data collection and analysis. Thematic analysis using inductive and deductive approaches was conducted. This study followed the COnsolidated criteria for REporting Qualitative research (COREQ) guidelines. Results Our findings revealed barriers and facilitators at the guideline, client, professional, professional interaction, professional client interaction, client interaction, organisational, community, and societal level. Six main themes covering multiple barriers and facilitators were identified: (1) guidelines’ applicability to (work)setting; (2) professionals’ cognitions and attitude towards IPC (related to educational background); (3) organisational support and priority; (4) educational system; (5) time availability and staff capacity; and (6) task division and change coaches. The main professional-reported recommendations were the introduction of tailored and practical IPC guidelines, structural IPC education and training among all professionals, and client participation. Conclusions To promote IPC, multifaceted and multilevel strategies should be implemented, with a preliminary need ...