Background CT head is commonly performed in the setting of delirium and altered mental status (AMS), with variable yield. We aimed to evaluate the yield of CT head in hospitalized patients with delirium and/or AMS across a variety of clinical settings and identify factors associated with abnormal imaging. Methods We included studies in adult hospitalized patients, admitted to the emergency department (ED) and inpatient medical unit (grouped together) or the intensive care unit (ICU). Patients had a diagnosis of delirium/AMS and underwent a CT head that was classified as abnormal or not. We searched Medline, Embase and other databases (informed by PRISMA guidelines) from inception until November 11, 2021. Studies that were exclusively performed in patients with trauma or a fall were excluded. A meta‐analysis of proportions was performed; the pooled proportion of abnormal CTs was estimated using a random effects model. Heterogeneity was determined via the I2 statistic. Factors associated with an abnormal CT head were summarized qualitatively. Results Forty‐six studies were included for analysis. The overall yield of CT head in the inpatient/ED was 13% (95% CI: 10.2%–15.9%) and in ICU was 17.4% (95% CI: 10%–26.3%), with considerable heterogeneity (I2 96% and 98% respectively). Heterogeneity was partly explained after accounting for study region, publication year, and representativeness of the target population. Yield of CT head diminished after year 2000 (19.8% vs. 11.1%) and varied widely depending on geographical region (8.4%–25.9%). The presence of focal neurological deficits was a consistent factor that increased yield. Conclusion Use of CT head to diagnose the etiology of delirium and AMS varied widely and yield has declined. Guidelines and clinical decision support tools could increase the appropriate use of CT head in the diagnostic etiology of delirium/AMS.