AbstractThis paper presents a modification of the tabu search called gradient tabu search (GTS). It uses analytical gradients for a fast minimization to the next local minimum and analytical diagonal elements of the Hessian to escape local minima. For an efficient blocking of already visited areas tabu regions and tabu directions are introduced into the tabu list (TL). Trials with various well‐known test functions indicate that the GTS is a very promising approach to determine local and global minima of differentiable functions. Possible application areas could be optimization routines for force field parameters or conformational searches for large molecules. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 601–611, 2007