Abstract Background Takotsubo Cardiomyopathy represents an acute transient decline in left ventricular (LV) function occurring in the absence of obstructive coronary artery disease or acute plaque rupture. Therapeutic strategies vary due to a paucity of evidence-based guidelines. Purpose To evaluate clinical and biochemical characteristics, management approach and outcomes in a contemporary cohort of patients with Takotsubo Cardiomyopathy across two tertiary centres in Victoria, Australia. Neurohormonal associations were explored by characterising the prevalence of pre-existing endocrinopathies and malignancy. Methods We conducted a retrospective study of 240 patients with Takotsubo Cardiomyopathy diagnosed between 2008–2018, utilising data from electronic medical records. Results Patients were predominantly female (91.3%, mean age 66±12 years), smokers (48.3%), and hypertensive (55.0%). A small proportion (16.7%) had pre-existing malignancy (breast 30%, gastrointestinal 23%, genitourinary 19%, lung 9%, other 19%) or endocrine disease (12.5%), largely driven by thyroid disease (94%). Troponin rise was common (94.6%; peak troponin 6.4±13μg/L), though few presented with ST-elevation (21.7%). Psychosocial stress was prevalent (44.6%) compared with physical illness (39.2%) or an unidentified precipitant (16.7%). Management was heterogeneous. Many were discharged on aspirin (37.7%), dual antiplatelet therapy (34%) or statins (35.9%) in the absence of obstructive coronary disease or other clinical indication and were frequently continued beyond 1 year. ACE inhibitors or angiotensin receptor blockers were prescribed in 83.7%, beta blockers in 84.9% or both in 74.9% (continuing beyond 1 year in 60.4%). LV dysfunction occurred in 81.7% at diagnosis (mean LV ejection fraction (LVEF) 45±11%), recovering in 91.3% (mean LVEF 62±8%; 17.2% increase, p<0.001) on repeat echocardiography (mean 107±154 days). Follow up occurred in 81.4%, though most patients with normalised LV function continued heart failure therapy (83.6%). 12-month mortality was rare (7%) as was recurrence (5.1%). Conclusions Management of Takotsubo Cardiomyopathy remains challenging due to phenotypic diversity, variable therapeutic approach and unclear treatment duration. Pre-existing illness, including malignancy and endocrinopathy, may provide a substrate for the development of Takotsubo Cardiomyopathy or amplify cardiac adrenoreceptor sensitivity. Enhanced understanding of possible neurohormonal and cellular mechanisms may facilitate targeted management and preventive strategies. The role of antiplatelets or lipid lowering therapy is not supported in existing literature, however, as this study highlights, they continue to feature heavily in the Takotsubo treatment armamentarium. Further studies are needed to enhance understanding of underlying mechanisms and establish a standardised treatment approach with targeted therapy to promote LV recovery and prevent recurrence. Acknowledgement/Funding None