Patients with ischemic heart disease (IHD) were frequently excluded from acute respiratory distress syndrome (ARDS) clinical studies. Consequently, nothing was understood about the effects of IHD in this population. For a study, researchers sought to determine the relationship between IHD and clinical outcomes in ARDS patients. Participants from 4 randomized controlled studies on acute respiratory distress syndrome (ARDS) with shared study criteria, definitions, and endpoints were included. Using multivariable logistic regression, investigators evaluated the relationship between IHD and the primary outcome of 60-day mortality. Secondary outcomes were mortality at 90 days, ventilator-free days at 28 days, and organ failure at 28 days. Among 1,909 individuals, 102 had a previous diagnosis of IHD (5.4%). Ischemic heart disease patients were more likely to be older and male (P<0.05). Noncardiac comorbidities, disease severity, and other indices of ARDS severity did not vary statistically (all, P>0.05). IHD patients had a higher 60-day (39.2% vs 23.3%, P<0.001) and 90-day (40.2% vs 24.0%, P<0.001) mortality rate, as well as a higher incidence of renal (45.1% vs 32.0%, P=0.006) and hepatic (35.3% vs 25.2%, P=0.023) failure. About 60-day (odds ratio [OR] 1.76; 95% CI: 1.07 to 2.89, P=0.025) and 90-day (odds ratio [OR] 1.74; 95% CI: 1.06 to 2.89, P=0.028) mortality remained elevated following multivariable adjustment. Ischemic heart disease was related with 10% fewer ventilator-free days (incidence rate ratio 0.90; 95% CI: 0.85 to 0.96; P=0.001). In conclusion, IHD was related to increased mortality and fewer ventilator-free days in ARDS patients. Future research was required to discover mortality predictors and enhance treatment paradigms for this subgroup of critically sick individuals.