Dopamine receptor blocking agents (DRBAs, also known as antipsychotics) are frequently used in hospitalized patients. These medications carry a significant side effect burden and should be used judiciously. This purpose of this study is to examine patient, disease, and medication characteristics associated with the use of DRBAs in the inpatient setting to better understand current prescribing patterns and opportunities for optimization. A retrospective analysis was performed of 17,224 patients with at least one inpatient DRBA order placed between 1/1/2018–12/31/2019. The study population at this community hospital network in the United States contained those with (71.0%) and without (29.0%) psychiatric diagnoses, and the mean number of DRBA medications for each patient was 2.4 +/− 1.1. The characteristics of single, male, government-sponsored health insurance, movement disorder, DRBA adverse effects, and medication non-adherence were associated with significantly greater mean total DRBA medications prescribed. Medication non-adherence and prescription of a long-acting injectable (LAI) DRBA were greater in single and male patients, while suicidality was more likely in those with a movement disorder or DRBA adverse effect. Specific agents were also significantly associated with cardiovascular disease and metabolic disorder diagnoses. Based on the findings of this study, several patient, disease, and medication factors are related to the use of DRBAs in the hospital setting. It is important to further explore these associations in order to determine the appropriateness of DRBA prescribing and identify areas for improvement.