Quantitative Structure Activity Relationship correlating the antitubercular and antibacterial (Staphylococcus aureus and Escherichia coli) activities with the structural descriptors of reported naphthyridine derivatives was developed. The data were divided into training and test sets. The former was used to develop the regression model and the latter was used to examine the predictive capability of these models. The statistical measures such as squared correlation coefficient (r 2 = 0.79-0.84), adjusted squared correlation coefficient (r 2 adj = 0.78-0.83) F-ratio (26.85-67.16), and cross-validation (q 2 = 0.74-0.79) were found to be satisfactory for all activities and the predictions were within the 99% confidence level. The models contained atom type, thermodynamic, structural, and electrotopological descriptors which emphasized the importance of the size, shape, and the lipophilicity of the molecule. © Springer Science+Business Media, LLC 2011.