Background: The digital transformation of health care is advancing rapidly. A well-accepted framework for health care improvement is the Quadruple Aim: improved clinician experience, improved patient experience, improved population health, and reduced health care costs. Hospitals are attempting to improve care by using digital technologies, but the effectiveness of these technologies is often only measured against cost and quality indicators, and less is known about the clinician and patient experience., Objective: This study aims to conduct a systematic review and qualitative evidence synthesis to assess the clinician and patient experience of digital hospitals., Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and ENTREQ (Enhancing the Transparency in Reporting the Synthesis of Qualitative Research) guidelines were followed. The PubMed, Embase, Scopus, CINAHL, and PsycINFO databases were searched from January 2010 to June 2022. Studies that explored multidisciplinary clinician or adult inpatient experiences of digital hospitals (with a full electronic medical record) were included. Study quality was assessed using the Mixed Methods Appraisal Tool. Data synthesis was performed narratively for quantitative studies. Qualitative evidence synthesis was performed via (1) automated machine learning text analytics using Leximancer (Leximancer Pty Ltd) and (2) researcher-led inductive synthesis to generate themes., Results: A total of 61 studies (n=39, 64% quantitative; n=15, 25% qualitative; and n=7, 11% mixed methods) were included. Most studies (55/61, 90%) investigated clinician experiences, whereas few (10/61, 16%) investigated patient experiences. The study populations ranged from 8 to 3610 clinicians, 11 to 34,425 patients, and 5 to 2836 hospitals. Quantitative outcomes indicated that clinicians had a positive overall satisfaction (17/24, 71% of the studies) with digital hospitals, and most studies (11/19, 58%) reported a positive sentiment toward usability. Data accessibility was reported positively, whereas adaptation, clinician-patient interaction, and workload burnout were reported negatively. The effects of digital hospitals on patient safety and clinicians' ability to deliver patient care were mixed. The qualitative evidence synthesis of clinician experience studies (18/61, 30%) generated 7 themes: inefficient digital documentation, inconsistent data quality, disruptions to conventional health care relationships, acceptance, safety versus risk, reliance on hybrid (digital and paper) workflows, and patient data privacy. There was weak evidence of a positive association between digital hospitals and patient satisfaction scores., Conclusions: Clinicians' experience of digital hospitals appears positive according to high-level indicators (eg, overall satisfaction and data accessibility), but the qualitative evidence synthesis revealed substantive tensions. There is insufficient evidence to draw a definitive conclusion on the patient experience within digital hospitals, but indications appear positive or agnostic. Future research must prioritize equitable investigation and definition of the digital clinician and patient experience to achieve the Quadruple Aim of health care., (©Oliver J Canfell, Leanna Woods, Yasaman Meshkat, Jenna Krivit, Brinda Gunashanhar, Christine Slade, Andrew Burton-Jones, Clair Sullivan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.03.2024.)