ABSTRACT: BACKGROUND:Past studies examining barriers to patient portal adoption have been conducted with a small number of patients and health care settings, limiting generalizability. OBJECTIVE:This study had the following two objectives: (1) to assess the prevalence of barriers to patient portal adoption among nonadopters and (2) to examine the association between nonadopter characteristics and reported barriers in a nationally representative sample. METHODS:Data from this study were obtained from the 2019 Health Information National Trends Survey. We calculated descriptive statistics to determine the most prevalent barriers and conducted multiple variable logistic regression analysis to examine which characteristics were associated with the reported barriers. RESULTS:The sample included 4815 individuals. Among these, 2828 individuals (58.73%) had not adopted a patient portal. Among the nonadopters (n=2828), the most prevalent barriers were patient preference for in-person communication (1810/2828, 64.00%), no perceived need for the patient portal (1385/2828, 48.97%), and lack of comfort and experience with computers (735/2828, 25.99%). Less commonly, individuals reported having no patient portal (650/2828, 22.98%), no internet access (650/2828, 22.98%), privacy concerns (594/2828, 21.00%), difficulty logging on (537/2828, 18.99%), and multiple patient portals (255/2828, 9.02%) as barriers. Men had significantly lower odds of indicating a preference for speaking directly to a provider compared with women (odds ratio [OR] 0.75, 95% CI 0.60-0.94; P=.01). Older age (OR 1.01, 95% CI 1.00-1.02; P<.001), having a chronic condition (OR 1.83, 95% CI 1.44-2.33; P<.001), and having an income lower than US $20,000 (OR 1.61, 95% CI 1.11-2.34; P=.01) were positively associated with indicating a preference for speaking directly to a provider. Hispanic individuals had significantly higher odds of indicating that they had no need for a patient portal (OR 1.59, 95% CI 1.24-2.05; P<.001) compared with non-Hispanic individuals. Older individuals (OR 1.05, 95% CI 1.04-1.06; P<.001), individuals with less than a high school diploma (OR 3.15, 95% CI 1.79-5.53; P<.001), and individuals with a household income of less than US $20,000 (OR 2.78, 95% CI 1.88-4.11; P<.001) had significantly higher odds of indicating that they were uncomfortable with a computer. CONCLUSIONS:The most common barriers to patient portal adoption are preference for in-person communication, not having a need for the patient portal, and feeling uncomfortable with computers, which are barriers that are modifiable and can be intervened upon. Patient characteristics can help predict which patients are most likely to experience certain barriers to patient portal adoption. Further research is needed to tailor implementation approaches based on patients' needs and preferences.