Objectives: This study determines the impact that use of personal digital assistants (PDAs) has on avoiding potential medication prescribing errors in primary care, office-based practices. The specific aims are to (1) measure the occurrence of prescribing-related errors, (2) determine the extent to which medication prescribing errors may be reduced by physicians having improved access to pharmaceutical information at the point of care via the PDA and use of the PDA as a prescription-printing device, and (3) identify perceived barriers to PDA use and successful strategies to overcome these barriers. Methods: A prospective, randomized, controlled trial of 78 physicians was conducted in 31 primary care, office-based practices to determine the impact of PDA use on medication prescribing errors. The intervention group was trained by case-simulation to use a PDA-based clinical drug information application at the point of care during the prescribing process, and enter and print prescriptions on a local printer via the PDA. The control group maintained their traditional prescribing practices throughout the study. Qualitative interviews were conducted with the intervention group to identify perceived barriers to PDA use and successful strategies to overcome these barriers. Results: The outcome indicates that voluntary use of the PDA results in substantial reductions in errors of legibility, omissions, and use of abbreviations and symbols. Variation in adoption of the PDA as both a prescribing device and a drug information tool was observed. Barriers and successful strategies to overcome the barriers to PDA use are identified. Conclusion: The PDA offers an effective method to bring prescribing safety to primary care, office-based practices.