Evidence regarding the relationship between age-adjusted Charlson comorbidity index (ACCI) and in-hospital mortality is limited. Therefore, the present study investigated whether there was an independent association between ACCI and in-hospital mortality in critically ill patients with cardiogenic shock (CS) after adjusting for other covariates (age, sex, history of disease, scoring system, in-hospital management, vital signs at presentation, laboratory findings and vasopressors). ACCI, calculated retrospectively after hospitalization between 2008 and 2019, was derived from intensive care unit (ICU) admissions at the Beth Israel Deaconess Medical Center (Boston, MA, USA). Patients with CS were classified into two categories based on predefined ACCI scores (low, <8; high, ≥8). Based on baseline ACCI, the risk of in-hospital mortality in patients with CS was calculated using a multivariate Cox proportional risk model, and the threshold effect was calculated using a two-piece linear regression model. The in-hospital mortality rate was ~1.5 times greater in the ACCI high group compared with that in the ACCI low group [hazard ratio (HR)=1.45; 95% confidence interval (CI), 1.14-1.86]. Additional analysis showed that ACCI had a curvilinear association with in-hospital mortality risk in patients with CS, with a saturation effect predicted at 4.5. When ACCI was >4.5, the risk of in-hospital CS death increased significantly with increasing ACCI (HR=1.122; 95% CI, 1.054-1.194). Overall, ACCI was an independent predictor of in-hospital mortality in ICU patients with CS. A non-linear relationship was revealed between ACCI and in-hospital mortality, where in-hospital mortality increased significantly when ACCI was >4.5.Copyright: © Wei et al.