We developed the 'Pragmatic Proxy Protocol' (PPP) to estimate the prevalence of hospital-acquired infection (HAI) by integrating our existing pharmacy serial point prevalence studies of anti-infective prescribing practices with electronic data on microbiological and radiographic markers of infection. Our method was evaluated against the standard Hospital Infection Society/Infection Control Nurses Association Protocol (HIP). In the non-surgical patients, PPP has a sensitivity of 1.00 [confidence interval (CI): 0.70-1.00] and specificity of 0.97 (CI: 0.93-0.99). PPP suggests that for non-surgical patients, the prevalence of HAI using HIP could be underestimated by 42%. PPP takes about two-thirds of the time of HIP (75 vs 106 h) and is at least one-third cheaper. It could easily be adapted to advances in electronic reporting and, with the development of Anti-infective Care Bundles, would increase its sensitivity for the detection of HAI in surgical patients. PPP could be used to increase the frequency of routine HAI surveillance to determine the overall burden of infection and assess the efficacy of intervention strategies in a timely manner allowing rapid, direct feedback and engagement with clinicians.