Some new substituted tetrahydroacridin-8-ones and diverse derivatives were synthesized by uncatalysed multi-component reaction of dimedone or cyclohexan-1,3-dione, alpha-naphthylamine and various (o,p,m)-substituted benzaldehydes. The in vitro anti-microbial activities of the prepared compounds were evaluated against some bacteria and fungi strains. The results suggested that, the products 2a-g and 4a-g exhibited good inhibitory effect against most of the tested organisms. Especially, 2f, 2g, 4f and 4g were shown to be most effective against Rhodotorula rubra and Aspergillus parasiticus and compounds 2a, 2c, 2g, 4f and 4g proved to be effective with MIC values in the range of 3.9-7.8 microg/ml.