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Programs and reforms to prevent healthcare-associated infections encounter structural barriers that affect their adoption and effective implementation. This article is based on interviews with 55 frontline healthcare providers, infection control and quality experts, and policymakers from 2010–2013 primarily in Vancouver, Canada. This article reports the perceptions of participants regarding the consequences that structural barriers, including physical structure, staffing levels, education, policy variations, and authority, have on their ability to prevent healthcare-associated infections. The findings suggest the need to shift more funding to preventative measures, such as more infection-prevention professionals, higher participation in quality programs and increased availability of isolation rooms to reduce healthcare-associated infections. In addition, leadership and resources are needed to expand (1) mandatory annual infection prevention education sessions to all hospital staff with point of care follow up, and (2) standardised, evidence-based antimicrobial stewardship clinical practice guidelines and policies. [ABSTRACT FROM AUTHOR]