OBJECTIVES: As myocardial fibrosis might be an important contributor to the association of obesity with left ventricular (LV) dysfunction and heart failure, we investigated the effects of spironolactone on LV function and serological fibrosis markers (procollagen type III N-terminal propeptide (PIIINP) and procollagen type I C-terminal propeptide (PICP)) in patients with obesity and abnormal LV performance. DESIGN: A prospective, randomised, double-blind, placebo-controlled study. SETTING: A university hospital. PATIENTS AND INTERVENTION: 113 patients (mean±SD age 58±8 years) with body mass index≥30, without any comorbidities, with impaired early diastolic mitral annular velocity, randomised to spironolactone 25 mg/day or placebo for 6 months. MAIN OUTCOME MEASURES: Echocardiographically derived indices of LV systolic (strain and strain rate) and diastolic (E velocity, tissue e' and E/e' ratio) function, myocardial reflectivity (calibrated integrated backscatter (IB)), and serum PICP and PIIINP. RESULTS: In the spironolactone group, significant improvements in myocardial deformation, peak early diastolic velocity (Em), E/e' and IB were noted with a simultaneous decrease in PICP and PIIINP. No corresponding alterations were found with placebo. Improvement in LV systolic function (increase in strain) was independently associated with baseline strain (β=-0.43, p<0.001), change in IB (β=0.26, p<0.02) and baseline PICP (β=0.24, p<0.04). Among the independent determinants of LV diastolic improvement were for increase in Em - baseline Em (β=-0.44, p<0.001) and baseline PICP (β=0.35, p<0.002), and for decrease in E/e' - baseline E/e' (β=-0.35, p<0.005) and change in PICP (β=0.25, p<0.04). CONCLUSIONS: In patients with obesity without other comorbidities, aldosterone antagonism improves LV function and myocardial acoustic properties, and reduces circulating procollagen levels. Beneficial changes in cardiac performance are independently predicted by baseline LV dysfunction and baseline disturbances, as well as treatment-induced improvements in fibrosis markers. CLINICAL TRIAL REGISTRATION: http://www.anzctr.org.au ACTRN12609000655246.