Abstract The rapid evolution of digital health emphasises the need for effective eHealth literacy (eHL) to ensure equitable access to health information and improve patient outcomes. This systematic review and meta-analysis aim to assess the effectiveness of eHL interventions, addressing the significant gap in knowledge about which strategies are most beneficial. Adhering to PRISMA guidelines, we systematically retrieved, quantitatively pooled and critically appraised available experimental evidence on the effectiveness of eHL interventions across different populations. PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched for studies reporting original quantitative outcomes of eHL, assessed by the eHealth Literacy Scale or other validated scales. Data were pooled using a random-effects model, with critical appraisal of the included studies. From the 504 records screened, 15 studies met the inclusion criteria. They encompass interventions targeting adults with chronic diseases (6 studies), older adults (5), and young people (4) and examine either individualistic or collaborative approaches (respectively, 9 and 5 studies, and 1 assessing both). The meta-analysis revealed significant improvements in eHL, both pre- vs post-intervention (UMD 5.81, 95%CI 3.38-8.26, N = 1,025) and experimental vs control groups (OR 3.65, 95%CI 2.06-6.46, N = 1,258). Meta-regression showed a significant correlation between pre/post-intervention outcomes and baseline eHL levels (slope=-0.91, p-value=0.009). Our findings support the effectiveness of tailored interventions in significantly enhancing eHL, providing key insights (role of baseline eHL levels and intervention approach) for intervention design and implementation that are adaptable to various demographic contexts. This research was supported by the National Plan for Complementary Investments to the NRRP Hub Life Science-Digital Health (PNC-E3-2022-23683267, DHEAL-COM).
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