BACKGROUND: Adolescents and young adults (AYAs) with sarcomas often receive high-dose doxorubicin (Dox), but data on early cardiotoxicity in this population are limited. OBJECTIVES: To prospectively evaluate early echocardiographic changes in AYAs with sarcoma treated with high-dose Dox. METHODS: AYAs (15-39 years) with sarcoma treated at a tertiary cancer centre (2018-22) were prospectively enroled. Echocardiograms were performed at baseline, 1 and 2 years after cancer therapy initiation and interpreted by a single cardiologist. The primary endpoint was a >10% absolute reduction in left ventricular ejection fraction (LVEF), an absolute LVEF <50%, or >10% decrease in LV wall thickness/dimension (LVWT/D) ratio from baseline. Secondary endpoints included longitudinal changes in cardiac structure, chamber volumes, systolic and diastolic function, and strain. RESULTS: Of 70 patients, 56 completed at least two of three study echocardiograms (median age 22.6 [IQR, 17.6-30.5] years; 41% female, 84% white). Median cumulative Dox dose was 450 (IQR, 370-450) mg/m2; 75% received dexrazoxane. The primary endpoint was met by 44.4% at 1 year and 27.5% at 2 years, driven primarily by LVWT/D ratio decline (37% at 1 year, 25% at 2 years), while significant LVEF decline was observed in 11.1% and 2.5%, respectively. Significant absolute changes at 1 year included LVEF (-2.73 ± 4.3%, P < .001), global longitudinal strain magnitude (-1.37 ± 2.56%, P = .002), septal e' (-1.75 ± 2.48 cm/s, P < .001), and lateral e' (-2.78 ± 3.44 cm/s, P < .001), persisting at 2 years. One patient (1.8%) developed ventricular fibrillation and heart failure with reduced ejection fraction, with LVEF recovery within 1 year. CONCLUSIONS: Over one-third of AYAs with sarcoma met the primary endpoint at 1 year, with half of these abnormalities persisting at 2 years, primarily driven by LVWT/D ratio reductions. Subclinical changes in strain and diastolic function were observed, reflecting the broad cardiac impact of high-dose Dox in this population.