Patients with aortic stenosis are often indicated to aortic valve replacement to relief pressure overload. After surgery, patients experience a myocardial response commonly known as reverse remodeling, where structural and functional recovery are expected. Notwithstanding, some patients exhibit an incomplete response, whose biological mechanisms remain poorly understood. The pericardial fluid can be safely collected during valve replacement and its proteome composition reflects heart’s pathophysiological status. Taking this into account, we characterized pericardial fluid proteome of patients with complete and incomplete reverse remodeling following a shotgun LC-MS/MS (Orbitrap Q Exactive HF MS) approach. We aimed to improve the current understanding of the mechanisms underlying an incomplete reverse remodeling and to pinpoint surrogate prognostic markers for this condition. In the future, this data can be important to develop tools for early prognosis of incomplete reverse remodeling and to adjust medical/pharmacological therapies to maximize recovery.