Background and importance Marked differences have been described between women and men in disease prevalence, clinical presentation, response to treatment and outcomes. However, such data are scarce in the acutely ill. An awareness of differences related to biological sex is essential for the success of clinical care and outcomes in patients presenting with acute dyspnea, the most frequent cause of emergency department (ED) admission. Objectives The aim of the present study was to assess the effect of biological sex on 1-year all-cause mortality in patients presenting with acute dyspnea to the ED. Design, settings and participants Consecutive adult patients presenting with acute dyspnea in two Lithuanian EDs were included. Clinical characteristics, laboratory data and medication use at discharge were collected. Follow-up at 1 year was performed via national data registries. Outcomes measure and analysis The primary outcome of the study was 1-year all-cause mortality. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model, with and without adjustment for the following confounders: age, systolic blood pressure, creatinine, sodium and hemoglobin. Main results A total of 1455 patients were included. Women represented 43% of the study population. Compared to men, women were older [median (interquartile range [IQR]) age 74 (65–80) vs. 68 (59–77) years, P < 0.0001]. The duration of clinical signs before admission was shorter for women [median (IQR) duration 4 (1–14) vs. 7(2–14) days, P = 0.006]. Unadjusted 1-year all-cause mortality was significantly lower in women (21 vs. 28%, P = 0.001). Adjusted HR of 1-year all-cause mortality was lower in women when compared to men [HR 0.68 (0.53–0.88), P = 0.0028]. Additional sensitivity analyses confirmed the survival benefit for women in subgroups including age greater and lower than 75 years, the presence of comorbidities and causes of dyspnea (cardiac or noncardiac). Conclusion Women have better 1-year survival than men after the initial ED presentation for acute dyspnea. Understanding the biological sex-related differences should lead toward precision medicine, and improve clinical decision-making to promote gender equality in health.