Third-generation cephalosporins possess broad spectrum and potent activities against Gram-positive and Gram-negative bacteria. In order to establish a general methodology for improving the oral bioavailability of third-generation cephalosporins, we designed and prepared a series of novel prodrugs of cefetamet using cefetamet pivoxil as a substrate by converting the amino group at the aminothiazole moiety into a series of acyloxymethyl carbamates. Several prodrugs showed higher oral bioavailability than an L-alanyl analogue of cefetamet pivoxil and comparable bioavailability to cefetamet pivoxil.