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Background: Post-stroke delirium (PSD) is a modifiable predictor for worse outcome in stroke. Knowledge of its risk factors would facilitate clinical management of affected patients, but recently updated national guidelines consider available evidence insufficient. Aims: The study aimed to establish risk factors for PSD incidence and duration using high-frequency screening. Methods: We prospectively investigated patients with ischemic stroke admitted within 24 h. Patients were screened twice daily for the presence of PSD throughout the treatment period. Sociodemographic, treatment-related, and neuroimaging characteristics were evaluated as predictors of either PSD incidence (odds ratios (OR)) or duration (PSD days/unit of the predictor, b), using logistic and linear regression models, respectively. Results: PSD occurred in 55/141 patients (age = 73.8 ± 10.4 years, 61 female, National Institutes of Health Stroke Scale (NIHSS) = 6.4 ± 6.5). Age (odds ratio (OR) = 1.06 (95% confidence interval (CI): 1.02–1.10), b = 0.08 (95% CI = 0.04–0.13)), and male gender (b = 0.99 (95% CI = 0.05–1.93)) were significant non-modifiable risk factors. In a multivariable model adjusted for age and gender, presence of pain (OR < sub > mvar = 1.75 (95% CI = 1.12–2.74)), urinary catheter (OR < sub > mvar = 3.16 (95% CI = 1.10–9.14)) and post-stroke infection (PSI; OR < sub > mvar = 4.43 (95% CI = 1.09–18.01)) were predictors of PSD incidence. PSD duration was impacted by presence of pain (b < sub > mvar = 0.49 (95% CI = 0.19–0.81)), urinary catheter (b < sub > mvar = 1.03 (95% CI = 0.01–2.07)), intravenous line (b < sub > mvar = 0.36 (95% CI = 0.16–0.57)), and PSI (b < sub > mvar = 1.60 (95% CI = 0.42–2.78)). PSD (OR = 3.53 (95% CI = 1.48–5.57)) and PSI (OR = 5.29 (95% CI = 2.92–7.66)) independently predicted inferior NIHSS at discharge. Insular and basal ganglia lesions increased the PSD risk about four- to eight-fold. Discussion/Conclusion: This study identified modifiable risk factors, the management of which might reduce the negative impact PSD has on outcome. [ABSTRACT FROM AUTHOR]