Background: The study protocol for a randomized trial serves as the origin of subsequent trial conduct and reporting. With the recent shift towards increased public access to trial protocols and their prospective registration, these documents will become increasingly available and important for systematic reviewers, regulatory bodies, and journals aiming to identify unacknowledged and potentially biased deviations introduced during the course of the trial or during data analysis and manuscript preparation. However, previous reviews have demonstrated that a high proportion of trial protocols lack information about important items such as primary outcomes, allocation concealment, power calculations, the roles of sponsors and investigators in trial conduct, and the academic freedom of investigators. These deficiencies are problematic in terms of transparency, critical appraisal, and the potential for selective reporting in the literature. Objectives: To develop evidence-based guidelines for key items to be addressed in the protocol of a randomized, parallel group trial. To facilitate the critical appraisal of trials included in systematic reviews by improving the information provided in trial protocols. Methods: An evidence-based checklist of key items to include in a trial protocol is being developed through a series of systematic reviews and a Delphi consensus process involving trialists, journal editors, ethicists, and methodologists. Results: To date, we have completed three rounds of electronic surveys and background systematic reviews. In December 2007, 17 participants representing a broad range of stakeholders attended the first SPIRIT meeting in Ottawa, Canada to develop consensus on a structured guide for protocols of parallel group trials. Based on the final results of this Delphi process, the SPIRIT checklist will be presented. Conclusions: The evidence-based SPIRIT guidelines will be of benefit to systematic reviewers and other key stakeholders by helping to improve the quality of trial protocols, facilitating the critical appraisal of trials, and enhancing transparency in the medical literature.