BACKGROUND: Universal Precautions (UPs) and more recently Standard Precautions have been widely promoted in high-income countries to protect health care workers (HCWs) from occupational exposure to blood and the consequent risk of infection with bloodborne pathogens. In low-income countries, the situation is very different: UPs are often practiced partially, if at all, thereby exposing the HCWs to unnecessary risk of infection. The aim of this study is to describe rural north Indian HCWs knowledge and understanding of UPs and identify predictors of compliance to target intervention programs appropriately. METHODS: A cross-sectional survey was undertaken, involving 266 HCWs (response rate, 87%) from 7 rural north Indian health care settings. Information was gathered regarding compliance with UPs and a range of other relevant variables that potentially influence compliance (eg, demographic information, perception of risk, knowledge of bloodborne pathogen transmission, perception of safety climate, and barriers to safe practice). RESULTS: Knowledge and understanding of UPs were partial, and UPs compliance was suboptimal, eg, only 32% wore eye protection when indicated, and 40% recapped needles at least sometimes. After controlling for confounding, compliance with UPs was associated with being in the job for a longer period, knowledge of bloodborne pathogen transmission, perceiving fewer barriers to safe practice and a strong commitment to workplace safety climate. CONCLUSION: Interventions to improve UPs compliance among HCWs in rural north India need to address not only their knowledge and understanding but also the safety climate created by the organizations that employ them.