(1) Background: Differences in health outcomes across populations are due to disparities in access to the social determinants of health (SDoH), such as educational level, household income, and internet access. With several positive outcomes reported with patient portal use, examining the associated social determinants of health is imperative. Objective: This study analyzed the association between social determinants of health—education, health insurance, household income, rurality, and internet access—and patient portal use among adults in the United States before and after the COVID-19 pandemic. (2) Methods: The research used a quantitative, retrospective study design and secondary data from the combined cycles 1 to 4 of the Health Information National Trends Survey 5 (N = 14,103) and 6 (N = 5958). Descriptive statistics and logistic regression were conducted to examine the association between the variables operationalizing SDoH and the use of patient portals. (3) Results: Forty-percent (40%) of respondents reported using a patient portal before the pandemic, and this increased to 61% in 2022. The multivariable logistic regression showed higher odds of patient portal utilization by women compared to men (AOR = 1.56; CI, 1.32–1.83), those with at least a college degree compared to less than high school education (AOR = 2.23; CI, 1.29–3.83), and annual family income of USD 75,000 and above compared to those <USD 20,000 (AOR = 1.59; CI, 1.18–2.15). Those with access to the internet and health insurance also had significantly higher odds of using their patient portals. However, those who identified as Hispanic and non-Hispanic Black and residing in a rural area rather than urban (AOR = 0.72; CI, 0.54–0.95) had significantly lower odds of using their patient portals even after the pandemic. (4) Conclusions: The social determinants of health included in this study showed significant influence on patient portal utilization, which has implications for policymakers and public health stakeholders tasked with promoting patient portal utilization and its benefits.
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