Background <p>Sex differences in cardiac arrest outcomes had been widely studied in out-of-hospital cardiac arrest (OHCA). However, limited research has explored the impact of sex on neurological outcomes of patients with in-hospital cardiac arrest (IHCA).</p> Objective <p>This study aimed to investigate the association between sex and neurological outcomes at hospital discharge in IHCA patients.</p> Methods <p>A retrospective cohort study analyzed 1,536 adult IHCA patients from National Taiwan University Hospital. Neurological outcomes were categorized as favorable (CPC 1–2) or poor (CPC 3–5). Propensity score matching and logistic regression adjusted for confounders, with sensitivity and subgroup analyses validating results.</p> Results <p>The female had significantly poorer neurological outcomes compared to the male (95.34% vs. 90.80%, <i>P</i> &lt; 0.001). Female sex was independently associated with poor neurological outcomes across multiple analytical approaches. In the unadjusted analysis, female patients demonstrated significantly higher odds of poor neurological outcomes (OR = 2.07, 95%CI: 1.34–3.22, <i>P</i> = 0.001). This association persisted after adjusting for clinical variables (Model 1: OR = 2.38, 95%CI: 1.40–4.03, <i>P</i> = 0.001) and propensity scores (Model 2: OR = 2.38, 95%CI: 1.39–4.01, <i>P</i> &lt; 0.001). In the propensity score-matched cohort (<i>n</i> = 1,180), the association strengthened, with the fully adjusted model showing the robust relationship (Model 3: OR = 2.77, 95%CI: 1.54–4.99, <i>P</i> &lt; 0.002). Sensitivity and subgroup analyses consistently supported these findings.</p> Conclusion <p>Female was independently associated with poor neurological outcomes in IHCA patients. The findings highlighted the need for further research to explore underlying mechanisms and develop sex-specific strategies to improve IHCA outcomes.</p>