OBJECTIVE: The reliable and valid capture of patient-reported outcomes (PROs) are becoming increasingly important endpoints for the pharmaceutical industry. PROs are data reported by the patient, and can include health-related quality of life, functional status, symptoms, pain, bother, satisfaction, work loss, reduced productivity, and the use of medical resources. These data, when included in studies, have traditionally been collected using paper-based methods. Technological advances in electronic data capture, such as handheld computers, internet-based solutions, and interactive voice-response systems, facilitate collecting PROs and are important new tools for clinical and outcomes researchers. Our objective was to examine compliance rates between a handheld computer diary system and a paper-based diary. METHODS: Eighty pain patients were randomly assigned to complete a three-week, diary-monitoring protocol using either a compliance-enhanced electronic diary system or a paper diary. The paper diary was covertly instrumented to allow for objective determination of when the diary was opened or closed. RESULTS: Participants submitted diary cards corresponding to 89% of assigned assessment times (±15 min). However, the electronic record indicated that actual compliance with the paper diary was only 11%, indicating a high level of faked compliance. On 32% of all study days the paper diary was not opened, yet reported compliance for these days exceeded 90%. Evidence for back and forward filling of paper diary cards was observed. For the compliance-enhanced electronic diary, the actual compliance rate was 93%. CONCLUSIONS: Data from paper-based diaries are of questionable validity, given that many of their entries are not completed as required by the protocol. Science-based electronic diaries can produce high rates of patient compliance in the field. Improved methods for data collection should encourage researchers in the pharmaceutical industry to aggressively evaluate electronic PRO (ePRO) data to help differentiate their products.