Background Understanding the constructs of knowledge behind clinical practices in low-resource rural health care settings with limited laboratory facilities and surveillance programs may help in designing resource-appropriate infection prevention and control education. Methods Multiple qualitative methods of direct observations, individual and group focus discussions, and document analysis were used to examine health care workers' knowledge of infection prevention and control practices in intravenous therapy, antibiotic therapy, instrument reprocessing, and hand hygiene in 10 rural Indonesian health care facilities. Results Awareness of health care-associated infections was low. Protocols were in the main based on verbal instructions handed down through the ranks of health care workers. The evidence-based knowledge gained across professional training was overridden by empiricism, nonscientific modifications, and organizational and societal cultures when resources were restricted or patients demanded inappropriate therapies. This phenomenon remained undetected by accreditation systems and clinical educators. Conclusion Rural Indonesian health care workers would benefit from a formal introduction to evidence-based practice that would deconstruct individual protocols that include nonscientific knowledge. To achieve levels of acceptable patient safety, protocols would have to be both evidence-based and resource-appropriate.