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Objective The purpose of this study was to better understand the impact of a preexisting diagnosis of rheumatoid arthritis (RA) on patient hospital outcomes in acute coronary syndrome (ACS) in comparison to traditional ACS risk factors. Methods This retrospective study protocol included 673 patients hospitalized with ACS in the HCA Healthcare West Florida Division from January 1, 2016, to December 31, 2023. Analysis via logistic regression and negative binomial regression compared associations between patients with ACS as primary diagnostic codes during their hospital admissions who also had RA, considering demographics like age, sex, and race. Patient encounters and diagnoses were identified using ICD-10 codes. Regression models were used for our analysis due to the straightforward computation, increased reproducibility, ability to use both categorical and continuous variables, and capability to convert diagnostic codes into binary variables. Traditional risk factors for ACS were also included in multivariate analyses. These included current tobacco use, former tobacco use, alcohol use disorder, elevated BMI, hyperlipidemia (HLD), and diabetes mellitus (DM). Pregnant patients, patients below 18 years of age, patients missing demographic information, and patients with other autoimmune conditions were excluded from the study. Results For RA, the odds of in-hospital mortality were not significantly 0.779 times as likely (p-value 0.2252, 95% CI (0.520, 1.167)), and 30-day readmission odds were not significantly 0.948 times as likely (p-value 0.5671, 95% CI (0.789, 1.139)). RA resulted in a 1.034-factor statistically insignificant increase in length of stay (LOS) (p-value 0.3369, 95% CI (0.965, 1.108)). For the traditional risk factors, odds of in-hospital mortality were 1.071 times as likely for every one-year increase in age (p-value <0.0001, 95% CI (1.065, 1.077)), 1.285 times as likely for current smokers (p-value 0.0020, 95% CI (1.096, 1.507)), 0.970 times as likely for every one-point increase in BMI (p-value <0.0001, 95% CI (0.961, 0.980)), 0.647 times as likely for patients with HLD (p-value <0.0001, 95% CI (0.576, 0.726)), and 1.349 times as likely for patients with DM (p-value <0.0001, 95% CI (1.212, 1.502)). Age, DM, and alcohol use disorder resulted in statistically significant increased 30-day readmission. Age, male sex, Black race, other non-Caucasian races, former tobacco use, current tobacco use, DM, and alcohol use disorder resulted in statistically significant increased LOS. Conclusions RA was surprisingly associated with decreased in-hospital mortality and 30-day readmission in the setting of ACS despite an associated increased LOS, which needs to be investigated further. In terms of statistical significance, there was no difference in these outcomes in patients with RA versus patients without RA. HLD was unexpectedly associated with a significant decrease in in-hospital mortality, which requires further investigation. Meanwhile, the traditional risk factors, except BMI and HLD, continued to show worse outcomes with statistical significance in the same patient population. Longitudinal follow-up and further clinical investigation of these patient encounters will likely shed more light on these associations. This knowledge may prevent over-utilization of time, equipment, and resources when addressing hospitalized patients with RA presenting with ACS, particularly in acute care settings.