Abstract Background/Introduction In the elderly with cardiovascular disease (CVD), maintaining muscle strength and physical function is essential for preventing adverse outcomes like falls and hospitalizations. The decline in lower limb strength signals increased morbidity and mortality risks. The 5-times sit-to-stand test (5STS) is a practical method for assessing lower limb strength, yet its predictive value for muscle weakness and prognosis in older CVD patients is underexplored. Purpose This study aims to elucidate the 5STS's role in identifying muscle weakness and its impact on the prognosis of older patients with CVD, offering insights for targeted interventions. Methods We included 3585 patients aged ≥ 65 years with CVD (mean age, 75.8 ± 6.6 years, 64.5% male) who underwent assessment of the 5STS before discharge. Maximal quadriceps isometric strength (QIS) was evaluated as a marker of lower limb strength and expressed relative to body weight (% body weight: BW). The primary outcome was all-cause mortality. We used the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for each sex to calculate the cut-off values of the 5STS for low QIS (male < 45%BW, female < 35%BW), which have been reported to be associated with prognosis. In addition, we performed Kaplan-Meier curves and Cox regression analyses in five groups defined by 5STS time quartile and 5STS inability to assess the prognostic significance of 5STS. Cox regression analysis was performed as a multivariate model including the following variables; age, sex, body mass index, acute coronary syndrome, heart failure, hypertension, diabetes, dyslipidemia, current smoker, prior myocardial infarction, prior heart failure, prior chronic obstructive pulmonary disease, prior dementia, albumin, hemoglobin, estimated glomerular filtration rate, C-reactive protein. Result Over a median follow-up of 2.23 years (interquartile range 0.87-4.52 years), 657 (18.3%) patients died. Kaplan-Meier analysis indicated that both slow 5STS performance and inability to execute the 5STS were significantly linked with poorer prognosis (log-rank p < 0.001, Figure 1). After comprehensive adjustment, the slowest quartile and inability to perform the 5STS were associated with significantly higher mortality rates compared to the fastest quartile (HR 1.34; 95% CI: 1.05-1.72; p = 0.021; HR: 2.28; 95% CI: 1.60-3.24; p < 0.001, Figure 2). The ROC AUC for 5STS in identifying low QIS was 0.75 (95% CI: 0.73-0.77) for males and 0.75 (95% CI: 0.72-0.77) for females, with cut-off times established at 9.71s for males and 9.48s for females. Conclusion The 5STS, assessable in diverse settings without specialized equipment and reflecting key clinical outcomes, could serve as a standard tool for evaluating lower limb function.