The syntheses of substituted piperazinyl pyridyl oxazolidinones 8–16 are described. Their in vitro activities against Gram-positive organisms such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus and enterococcus were evaluated by minimum inhibitory concentration (MIC) determination. Compound 8 and 10 were found to be superior to linezolid.