Neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) is a member of the NEDD4 family of HECT E3 ubiquitin ligases. NEDD4 is highly expressed in cardiomyocytes, but its specific function in adult cardiomyocytes is unknown. To study the role of NEDD4 in adult cardiomyocytes, we have generated a Nedd4 floxed mouse model and crossed it with tamoxifen-inducible aMHC-MerCreMer mice to generate an inducible Nedd4 cardiomyocyte-specific knockout mouse model (Nedd4 icKO). In this study, we performed comprehensive molecular and cardiac physiological studies on Nedd4 icKO mice. Our results show that after performing age-dependent studies, cardiac function and structure were not dramatically altered in Nedd4 icKO mice, suggesting that the loss of NEDD4 did not cause cardiomyopathy. Further experiments revealed that the levels of chaperone proteins and the levels of global ubiquitination were not changed within the cardiac tissue of Nedd4 icKO mice. Together, these results suggest that deletion of NEDD4 in adult cardiomyocytes does not cause overt cardiomyopathy.