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The nationwide epidemiological data on Kounis Syndrome (KS), still remains indistinct in the United States (US) after it was first reported in 1991. We assessed the prevalence of KS among patients primarily hospitalized for allergic/hypersensitivity/anaphylactic reactions. We then compared baseline demographics, comorbidities, and outcomes of KS with patients with only allergic/hypersensitivity/anaphylactic reactions using the National Inpatient Sample, 2007–2014. The cohort comprised of 235,420 patients primarily hospitalized with allergy/hypersensitivity/anaphylactic reactions. Of these, 2616 [1.1%; 0.2% unstable angina, 0.2% ST-elevation myocardial infarction & 0.7% non-ST-elevation myocardial infarction] patients experienced ACS and were identified as having KS. Patients with KS were older (mean 65.9 ± 14.1 vs. 57.2 ± 17.8 yrs), more often White (71.1% vs. 58.6%), male (46.4% vs. 39.9%) and Medicare enrollees (58.9% vs. 41.5%) admitted non-electively (96.8% vs. 95.3%) as compared to non-KS group (p < 0.001). The hospitalizations with KS demonstrated higher all-cause in-hospital mortality (7.0% vs. 0.4%, p < 0.001), prolonged hospitalization stay (mean 5.8 ± 6.0 vs. 3.0 ± 3.9 days, p < 0.001), higher hospitalization charges ($52,656 vs. $20,487, p < 0.001) and more frequent transfers to other facilities. The rates of stroke (1.0% vs. 0.2%), arrhythmias (30.4% vs. 12.4%), venous thromboembolism (1.6% vs. 1.0%), and diagnostic and therapeutic coronary interventions were also found to be significantly higher in patients with KS (p < 0.05). Patients with KS had increased odds of in-hospital mortality [unadjusted OR: 18.52; 95% CI: 15.74–21.80, p < 0.001 & adjusted OR: 9.74, 95% CI: 8.08–11.76, p < 0.001] compared to non-KS group. Overall US prevalence of KS among patients hospitalized for allergic/hypersensitivity/anaphylactic reactions is 1.1% with a subsequent all-cause inpatient mortality rate of 7.0%. • Total of 235,420 hospitalizations occurred with allergic/hypersensitivity/anaphylactic reactions from 2007-2014. • Prevalence of KS among these patients was 1.1% [0.2% UA, 0.2% STEMI & 0.7% NSTEMI] with all-cause mortality of 7.0%. • KS patients were older more often White, male and admitted non-electively as compared to non-KS group. • The KS group demonstrated higher in-hospital mortality (7.0% vs. 0.4%) as compared to the non-KS group. • Rates of stroke (1.0% vs.0.2%), arrhythmia (30.4% vs. 12.4%) and VTE (1.6% vs. 1.0%) were significantly higher in KS group. • The KS group had higher rates of coronary interventions and resource utilization as compared to the non-KS group. [ABSTRACT FROM AUTHOR]