ImportanceMany health care systems are investing resources in identifying social determinants of health (SDoH) needs and facilitating interventions among the populations they serve. Because self-reported SDoH information is lacking, area-level measures are often used to estimate needs and direct resources.ObjectiveTo describe the large-scale deployment of SDoH assessments by a health system and determine the extent to which self-reported SDoH needs identified therein are associated with census tract–level social vulnerability measured using the Social Vulnerability Index (SVI).Design, Setting, and ParticipantsThis cross-sectional study assessed SDoH needs between January 1, 2020, and April 30, 2023, in both payer and clinical care settings. Modalities included telephonic outreach, face-to-face clinical interactions, self-entry into a tablet or kiosk, and web-based survey tools. Participants included individuals who responded to the assessment and had sufficient information for census tract identification. Respondents included both Highmark Health Plan members and nonmembers. Health plan members responded to the assessment through health plan programs or platforms, and both members and nonmembers responded to assessments during inpatient or outpatient encounters with the affiliated health system.Main Outcomes and MeasuresOverall and domain-specific SDoH needs self-reported through assessments, and severity and complexity of needs identified. Residential social vulnerability measures included overall SVI and the 4 conceptual themes comprising overall SVI.ResultsIn total, 841 874 assessments were recorded for 401 697 individuals (55.1% women; median [IQR] age, 55 [41-70] years). Social determinants of health needs were identified in 120 769 assessments (14.3%). Across all SDoH domains, increasing SVI was associated with a higher positivity rate (eg, 11.2% of those residing in the lowest-risk SVI quintile reported a need compared with 22.7% among those residing in the highest-risk quintile). Associations varied by SDoH domain and SVI theme. After adjusting for demographic and screening characteristics, odds of positive screening among those residing in the highest-risk SVI quintile were 1.74 (95% CI, 1.62-1.86) to 3.73 (95% CI, 3.48-4.00) times the odds among those residing in lowest risk quintile.Conclusions and RelevanceIn this cross-sectional study, the overall level of SDoH needs generally corresponded to area-level vulnerability. Some SDoH domains appeared far more sensitive to community characteristics than others. Notably, even among individuals from the highest-risk areas, the positive screening rate was roughly 1 in 4. These findings underscore the importance of individual-level SDoH data for service provision planning and health services research.