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Objective: To identify risk factors for delirium among hospitalized patients in Zambia. Methods: We conducted a prospective cohort study at the University Teaching Hospital in Lusaka, Zambia, from October 2017 to April 2018. We report associations of exposures including sociodemographic and clinical factors with delirium over the first three days of hospital admission, assessed using a modified Brief Confusion Assessment Method (bCAM). Findings: 749 patients were included for analysis (mean age, 42.9 years; 64.8% men; 47.3% with HIV). In individual regression analyses of potential delirium risk factors adjusted for age, sex and education, factors significantly associated with delirium included being divorced/widowed (OR 1.64, 95% CI 1.09–2.47), lowest tercile income (OR 1.58, 95% CI 1.04–2.40), informal employment (OR 1.97, 95% CI 1.25–3.15), untreated HIV infection (OR 2.18, 95% CI 1.21–4.06), unknown HIV status (OR 2.90, 95% CI 1.47–6.16), history of stroke (OR 2.70, 95% CI 1.15–7.19), depression/anxiety (OR 1.52, 95% CI 1.08–2.14), alcohol overuse (OR 1.96, 95% CI 1.39–2.79), sedatives ordered on admission (OR 3.77, 95% CI 1.70–9.54), severity of illness (OR 2.00, 95% CI 1.82–2.22), neurological (OR 7.66, 95% CI 4.90–12.24) and pulmonary-system admission diagnoses (OR 1.91, 95% CI 1.29–2.85), and sepsis (OR 2.44, 95% CI 1.51–4.08). After combining significant risk factors into a multivariable regression analysis, severity of illness, history of stroke, and being divorced/widowed remained predictive of delirium (p<0.05). Conclusion: Among hospitalized adults at a national referral hospital in Zambia, severity of illness, history of stroke, and being divorced/widowed were independently predictive of delirium. Extension of this work will inform future efforts to prevent, detect, and manage delirium in low- and middle-income countries. [ABSTRACT FROM AUTHOR]