Background Delays in patient discharge can not only lead to deterioration, especially among geriatric patients, but also incorporate unnecessary resources at the hospital level. Many of these delays and their negative impact may be preventable by early focused screening to identify patients at risk for transfer to a post-acute care facility. Early interprofessional discharge planning is crucial in order to fit the appropriate individual discharge destination. While prediction of discharge to a post-acute care facility using post-acute care discharge score, the self-care index, and a combination of both has been shown in a single-center pilot study, an external validation is still missing. Objective This paper outlines the study protocol and methodology currently being used to replicate the previous pilot findings and determine whether the post-acute care discharge score, the self-care index, or the combination of both can reliably identify patients requiring transfer to post-acute care facilities. Methods This study will use prospective data involving all phases of the quasi-experimental study “In-HospiTOOL” conducted at 7 Swiss hospitals in urban and rural areas. During an 18-month period, consecutive adult medical patients admitted to the hospitals through the emergency department will be included. We aim to include 6000 patients based on sample size calculation. These data will enable a prospective external validation of the prediction instruments. Results We expect to gain more insight into the predictive capability of the above-mentioned prediction instruments. This approach will allow us to get important information about the generalizability of the three different models. The study was approved by the institutional review board on November 21, 2016, and funded in May 2020. Expected results are planned to be published in spring 2021. Conclusions This study will provide evidence on prognostic properties, comparative performance, reliability of scoring, and suitability of the instruments for the screening purpose in order to be able to recommend application in clinical practice. International Registered Report Identifier (IRRID) DERR1-10.2196/21447