Mef2c belongs to the myocyte enhancer factor 2 (MEF2) family of MADS-box containing transcription factors, which have been shown to be important for various processes involved in cell differentiation, cell survival, and apoptosis. Previous gene-targeting studies have demonstrated a role for mef2c in early heart development since mice lacking mef2c die at embryonic day 9.5 due to cardiac and vascular defects. Since the early embryonic lethality of mef2c prevents an examination of its role in the later stages of heart development, conditional mef2c(loxP/loxP) mice were generated to allow for temporal- and tissue-specific analyses. We report here that general Cre recombinase-mediated removal of the second coding exon of mef2c phenocopied the original mef2c null. Additionally, myocardial-specific removal of mef2c resulted in viable offspring, demonstrating that while mef2c is required for the early development of the heart, it is not necessary for the formation of the heart after looping morphogenesis.