Healthcare analytics has traditionally relied upon linear and logistic regression models to address clinical research questions mostly because they produce highly interpretable results [1, 2]. These results contain valuable statistics such as p-values, coefficients, and odds ratios that provide healthcare professionals with knowledge about the significance of each covariate and exposure for predicting the outcome of interest [1]. Thus, they are often favored over new deep learning models that are generally more accurate but less interpretable and scalable. However, the statistical power of linear and logistic regression is contingent upon satisfying modeling assumptions, which usually requires altering or transforming the data, thereby hindering interpretability. Thus, generalized additive models are useful for overcoming this limitation while still preserving interpretability and accuracy. The major research question in this work involves investigating whether particular sedative agents (fentanyl, propofol, versed, ativan, and precedex) are associated with different discharge dispositions for patients with acute traumatic brain injury (TBI). To address this, we compare the effectiveness of various models (traditional linear regression (LR), generalized additive models (GAMs), and deep learning) in providing guidance for sedative choice. We evaluated the performance of each model using metrics for accuracy, interpretability, scalability, and generalizability. Our results show that the new deep learning models were the most accurate while the traditional LR and GAM models maintained better interpretability and scalability. The GAMs provided enhanced interpretability through pairwise interaction heat maps and generalized well to other domains and class distributions since they do not require satisfying the modeling assumptions used in LR. By evaluating the model results, we found that versed was associated with better discharge dispositions while ativan was associated with worse discharge dispositions. We also identified other significant covariates including age, the Northeast region, the Acute Physiology and Chronic Health Evaluation (APACHE) score, Glasgow Coma Scale (GCS), and ethanol level. The versatility of versed may account for its association with better discharge dispositions while ativan may have negative effects when used to facilitate intubation. Additionally, most of the significant covariates pertain to the clinical state of the patient (APACHE, GCS, etc.) whereas most non-significant covariates were demographic (gender, ethnicity, etc.). Though we found that deep learning slightly improved over LR and generalized additive models after fine-tuning the hyperparameters, the deep learning results were less interpretable and therefore not ideal for making the aforementioned clinical insights. However deep learning may be preferable in cases with greater complexity and more data, particularly in situations where interpretability is not as critical. Further research is necessary to validate our findings, investigate alternative modeling approaches, and examine other outcomes and exposures of interest. / Master of Science / Patients with Traumatic Brain Injury (TBI) often require sedative agents to facilitate intubation and prevent further brain injury by reducing anxiety and decreasing level of consciousness. It is important for clinicians to choose the sedative that is most conducive to optimizing patient outcomes. Hence, the purpose of our research is to provide guidance to aid this decision. Additionally, we compare different modeling approaches to provide insights into their relative strengths and weaknesses. To achieve this goal, we investigated whether the exposure of particular sedatives (fentanyl, propofol, versed, ativan, and precedex) was associated with different hospital discharge locations for patients with TBI. From best to worst, these discharge locations are home, rehabilitation, nursing home, remains hospitalized, and death. Our results show that versed was associated with better discharge locations and ativan was associated with worse discharge locations. The fact that versed is often used for alternative purposes may account for its association with better discharge locations. Further research is necessary to further investigate this and the possible negative effects of using ativan to facilitate intubation. We also found that other variables that influence discharge disposition are age, the Northeast region, and other variables pertaining to the clinical state of the patient (severity of illness metrics, etc.). By comparing the different modeling approaches, we found that the new deep learning methods were difficult to interpret but provided a slight improvement in performance after optimization. Traditional methods such as linear regression allowed us to interpret the model output and make the aforementioned clinical insights. However, generalized additive models (GAMs) are often more practical because they can better accommodate other class distributions and domains.