Loneliness and all-cause mortality in the United States.

IMPORTANCE: Loneliness affects more than half of US adults and has been declared a public health epidemic, yet whether clinically documented loneliness independently predicts mortality across diverse populations remains unclear. OBJECTIVE: To examine the association between clinically documented loneliness and all-cause mortality at 1, 3, and 5 years, overall and by sex, race and ethnicity, and age. METHODS: We conducted a propensity score-matched retrospective cohort study using the TriNetX US Collaborative Network, comprising electronic health record data from 65 health care organizations. Adults aged 18-90 years with at least one clinical encounter between January 1, 2016, and December 31, 2022, were eligible. Patients with a clinically documented diagnosis of loneliness were matched 1:1 (n = 28,944 per group) on age, sex, race and ethnicity, and 12 comorbidity domains to comparison patients with outpatient engagement and no loneliness diagnosis. The primary outcome was all-cause mortality at 1, 3, and 5 years. Between-group differences were assessed using risk differences, Kaplan-Meier survival analysis, and Cox proportional hazards models, overall and across prespecified subgroups. RESULTS: Among 57,888 matched adults (mean age, 55.4 years; 62.9% female), loneliness was associated with increased mortality at every horizon: 1-year hazard ratio (HR), 1.52 (95% CI, 1.40-1.66); 3-year HR, 1.35 (95% CI, 1.27-1.43); and 5-year HR, 1.29 (95% CI, 1.22-1.35). Absolute survival gaps widened from 1.57 to 2.82 percentage points. The largest 1-year relative excess occurred among male patients (HR, 1.85) and Hispanic patients (risk ratio, 2.33). Black patients had the greatest 3-year absolute gap (2.49 percentage points). Working-age adults showed sustained excess hazard across all windows (HR, 1.34-1.42), whereas older adults had the largest 1-year absolute gap (2.28 percentage points) with convergence by 5 years. CONCLUSION: Clinically documented loneliness was independently associated with increased all-cause mortality at 1, 3, and 5 years, with the burden varying by sex, race and ethnicity, and age. These findings identify loneliness as a measurable, independent mortality risk marker and suggest that routine screening and targeted psychosocial intervention warrant prospective evaluation.