In this study, 4(1H)-pyridinones with an amide function in Position 2 of the pyridinone ring showed antimicrobial activity. The synthesis and the biological properties of some novel amide derivatives of pyran-4(1H)-one and 4(1H)-pyridinone have been reported. Amide derivatives of pyran-4(1H)-one and 4(1H)-pyridinone were prepared using two different methods. Antimicrobial activities were determined as MIC values using the microdilution broth method against the bacteria Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa and the fungi Candida albicans, Candida krusei and Candida parapsilosis. Compounds 6 and 9 exhibited the best inhibitor activity against S. aureus.