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Introduction: Myocardial dysfunction and the presence of calcified and non-calcified coronary plaques are predictors of cardiovascular disease. Masculinizing gender-affirming hormone therapy may increase cardiovascular risk, highlighting the need for prospective studies to evaluate cardiovascular outcomes during gender-affirming hormone therapy., Objectives: To evaluate changes in cardiac morphology, systolic and diastolic function, and development of coronary plaques after masculinizing gender-affirming hormone therapy., Methods: Prospective study including 47 transmasculine persons (gender-affirming hormone therapy-naïve, TransM&#95;TN, n = 15 and gender-affirming hormone therapy-ongoing, TransM&#95;TO, n = 32). Included persons were evaluated at study inclusion and after one year of masculinizing gender-affirming hormone therapy. At baseline, the median age of TransM&#95;TN was 22 years (interquartile range 19-28 years) and TransM&#95;TO 26 years (interquartile range 24-37 years) with a median gender-affirming hormone therapy duration of 4 years (interquartile range 2-5 years). Cardiac morphology including left ventricular wall thickness, volume, and mass, as well as left ventricular systolic and diastolic function was evaluated using echocardiography. Coronary artery calcifications and non-calcified coronary plaque were assessed using coronary computed tomography angiography. Paired and unpaired statistical analyses were performed within and between TransM&#95;TN and TransM&#95;TO groups., Results: In TransM&#95;TN, diastolic function decreased during follow-up with decreased septal and lateral left ventricular relaxation (14-11 cm/s, p = 0.04 and 18-15 cm/s, p = 0.02, respectively). No significant changes were observed in cardiac morphology, systolic function, or formation of coronary artery calcifications and non-calcified coronary plaque in TransM&#95;TN or TransM&#95;TO groups. At baseline, left ventricular end-diastolic internal diameter was significantly higher in TransM&#95;TO compared to TransM&#95;TN, 4.6 cm (interquartile range 4.3-5.0 cm) versus 4.4 cm (interquartile range 4.2-4.6 cm), p < 0.05. Other baseline cardiac outcomes were comparable between TransM&#95;TN and TransM&#95;TO., Conclusion: Diastolic function declined after the initiation of masculinizing gender-affirming hormone therapy and individuals on long-term masculinizing gender-affirming hormone therapy had larger left ventricular dimensions compared to individuals before gender-affirming hormone therapy initiation. Cardiac morphology, systolic function, and coronary plaque formation remained stable during masculinizing gender-affirming hormone therapy., (© 2025 The Author(s). Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology and European Academy of Andrology.)