Background: Sign-out is a mechanism of transferring information, responsibility, and authority from one set of caregivers to another. In teaching hospitals, sign-out between resident physicians has a long tradition. Because of the need to reduce the number of hours residents spend in the hospital, the number of sign-outs has increased, while continuity of care during hospital stays has decreased. As a result, when caring for hospitalized patients, residents have become increasingly dependent upon exchange of information during sign-out. Despite its critical importance, little research has examined the content, process, and effectiveness of resident sign-out. Even less is known about how sign-out should be conducted or how interventions might improve the quality of sign-out. Methods: Between October 2005 and February 2006, and again between October 2006 and February 2007, residents completed a post-call survey immediately after a call shift; we also audio-recorded sign-out sessions. Results: At baseline, an unexpected event arose during one-third of call shifts that should have been anticipated and discussed during sign-out. Recordings demonstrated sign-out was informal and unstructured with very wide variation in the type and extent of information exchanged. Based on these results, we explicitly defined the goals of sign-out; characterized information needed for concise, complete, and consistent sign-out; outlined a structured process to enhance the quality and efficiency of information exchange; developed a computerized tool to facilitate the process; and developed a curriculum to train residents how to sign-out more effectively. After implementing the new process and computer tool, the percentage of call nights when an unexpected event arose that should have been anticipated and discussed during sign-out was nearly identical to that at baseline. Conclusion: Although resident physicians frequently sign-out to one another, there are many times when important information is not transmitted. Future studies should be directed at identifying the information physicians need while on-call and clearly describing the goals and characteristics of a concise and complete sign-out. Additional studies are also needed to identify how to best teach and evaluate a physician’s ability to sign-out and how technology can be employed most effectively and appropriately.