To assess the acceptability and usage of a standalone personal digital assistant (PDA)-based clinical decision-support system (CDSS) for the diagnosis and management of acute respiratory tract infections (RTIs) in the outpatient setting.Observational study performed as part of a larger randomized trial in six rural communities in Utah and Idaho from January 2002 to March 2004. Ninety-nine primary care providers received a PDA-based CDSS for use at the point-of-care, and were asked to use the tool with at least 200 patients with suspected RTIs.Clinical data were collected electronically from the devices at periodic intervals. Providers also completed an exit questionnaire at the end of the study period.Providers logged 14,393 cases using the CDSS, the majority of which (n=7624; 53%) were from family practitioners. Overall adherence with CDSS recommendations for the five most common diagnoses (pharyngitis, otitis media, sinusitis, bronchitis, and upper respiratory tract infection) was 82%. When antibiotics were prescribed (53% of cases), adherence with the CDSS-recommended antibiotic was high (76%). By logistic regression analysis, the odds of adherence with CDSS recommendations increased significantly with each ten cases completed (P=0.001). Questionnaire respondents believed the CDSS was easy to use, and most (44/65; 68%) did not believe it increased their encounter time with patients, regardless of prior experience with PDAs.A standalone PDA-based CDSS for acute RTIs used at the point-of-care can encourage better outpatient antimicrobial prescribing practices and easily gather a rich set of clinical data.