Background: Cardiovascular disease remains the leading cause of death in the United States. Coronary artery disease alone accounted for approximately 13% of deaths in the US in 2016. Some studies have suggested an increased prevalence of coronary artery disease (CAD) in chronic inflammatory conditions, such as celiac disease (CD). Chronic subclinical systemic inflammation, decreased absorption of cardio-protective nutrients and drugs have all been postulated as the driving mechanisms for this increased risk of CAD. Methods: We reviewed a Nationwide Inpatient Sample from 2007 to 2017, using Acute Coronary syndrome as a principal diagnosis with CD as the secondary diagnosis, utilizing validated ICD-9-CM and ICD-10 codes. We examined the annual trends in the number of cases and hospitalization charges yearly and used survey regression to calculate adjusted odds ratios (aOR) for hospital mortality and other outcomes. Results: We identified a total of 8,036,307 ACS hospitalizations from 2007 to 2017, of which 5917 (0.07%) had a diagnosis for CD. The proportion of patients with CD in ACS hospitalizations increased from 0.015% in 2007 to 0.076% in 2017. These patients were significantly older (70.3 vs. 67.4 years, p
< 0.02), more likely female (51.9% vs. 39.5%, p
< 0.01), and more likely to be white (93.8% vs. 76.6%; p
< 0.01) than ACS patients without CD. After adjusting for age, gender, race, Charlson Comorbidity index and hospital level characteristics, ACS hospitalizations for CD patients had a lower odds ratio for hospital mortality (aOR = 0.39; 95% CI = 0.23–0.67; p
< 0.01). Additionally, length of stay in this patient population was shorter (4.53 vs. 4.84 days, p
< 0.01) but the mean hospitalization charges were higher (USD 64,058 vs. USD 60,223, p
< 0.01). Conclusion: We found that the number of ACS-related admissions in CD patients has risen more than five-fold between 2007 and 2017. However, the odds of in-hospital mortality in these patients is not higher than patients without CD. The results of our study demonstrate that although the systemic inflammation related to CD is associated with an increasing prevalence of ACS hospitalizations, on the contrary, the mortality rate is significantly higher in patients without celiac disease.