Independent studies have shown either ubiquitin‐mediated protein degradation or the mammalian target of rapamycin (mTOR) is necessary for increased ventricular mass and survival signaling for compensated hypertrophy in pressure‐overloaded (PO) myocardium. We tested whether the ubiquitin‐mediated regulation of growth and survival in hypertrophic myocardium is linked to the mTOR pathway. For in vivo studies, right ventricle pressure overload (RVPO) in rats was conducted by pulmonary artery banding; the normally loaded LV served as an internal control. Rapamycin (0.75 mg/kg/day) or vehicle alone was administered intraperitoneally for 3 days or 2 wk. Ubiquitinated proteins increased in cardiomyocytes following 48 h PO and were further enhanced by rapamycin. Rapamycin pretreatment also significantly increased PO‐induced Akt phosphorylation at S473, confirmed in cardiomyocytes in vitro to be downstream of mTORC2. In vivo prosurvival signaling showed rapamycin increased PO‐induced degradation of phosphorylated inhibitor of κB (IκB), enhanced expression of cellular inhibitor of apoptosis protein 1 (cIAP1), and decreased active caspase‐3. Long term rapamycin treatment in 2 wk PO myocardium blunted hypertrophy, improved contractile function, and reduced caspase‐3 and calpain activation. Therefore, rapamycin may have cardioprotective benefits for hypertensive patients.