A series of esters and amides of myristic acid was synthesized and tested in vitro for antibacterial activity against gram-positive and gram-negative bacteria. All the compounds showed activity comparable to that of the standard drug, ciprofloxacin. The structural characteristics governing antibacterial activity of myristic acid derivatives was studied using QSAR methodology. The results showed that the antibacterial activity could be modeled using the topological descriptor, valence molecular connectivity index. The predictive ability of the models was cross-validated by construction of a test set. The low residual activity and high cross-validated r2 values (r(cv)2) observed indicated the predictive ability of the developed QSAR models.