Background <p>Respiratory failure occurs frequently in cardiogenic shock but with varying severity. It is unknown whether invasive ventilation should be used strictly, reserved for severe respiratory failure, or liberally, reducing stress and increasing compliance with intensive care procedures. Aim of this study was to evaluate the impact of invasive ventilation on outcomes in patients with heart failure-related cardiogenic shock across the severity of respiratory failure.</p> Methods <p>Patients with heart failure-related cardiogenic shock treated 2010–2021 in 16 tertiary care centers in five countries were enrolled. Cox regression models were constructed to assess the impact of overall invasive ventilation and invasive ventilation stratified by PaO₂/FiO₂ ≤ 100, 101–200, and &gt; 200 on 30-day mortality, adjusted for relevant confounders. </p> Results <p>Of <i>N</i> = 1010 patients (median age 64&#xa0;years, 724 (71.7%) male), 659 patients (65.2%) received invasive ventilation. In patients receiving invasive ventilation, 30-day mortality was 1.67 times higher (95% confidence interval (CI) 1.26–2.22, <i>p</i> &lt; 0.001) than in patients without invasive ventilation. Although patients with a worse PaO₂/FiO₂ of ≤ 100 and 101–200 had the highest mortality risk (hazard ratio (HR) 1.74, 95% CI 1.19–2.53, <i>p</i> = 0.004 and HR 1.82, 95% CI 1.29–2.56, <i>p</i> &lt; 0.001), the same trend towards increased mortality persisted even in patients with preserved gas exchange and PaO₂/FiO₂ &gt; 200 (HR 1.39, 95% CI 0.99–1.97, <i>p</i> = 0.06).</p> Conclusions <p>In patients with cardiogenic shock, invasive ventilation was associated with higher mortality, with a non-significant trend towards higher mortality even in patients with preserved gas exchange. The results call for further analyses on this topic, specifically to clarify whether dedicated ventilator settings or weaning strategies may improve outcomes for affected patients.</p> Graphical abstract <p></p>