This study investigated the effects of process parameters on acceleration amplitude in the drilling of AISI D2 and AISI D3 cold work tool steels using HSS twist drills of two different lengths. Workpiece hardness, drill length/tool overhang, cutting speed, feed rate, and number of holes drilled were chosen as the process parameters. In the tests made by using the full factorial (FF) design technique, the values of induced machining vibrations occurring on the workpiece during drilling were specified as the acceleration amplitude. Measurement results were evaluated by linear regression analysis, and a second-order equation was developed for the prediction of the acceleration amplitude. The correlation coefficient of the predictive equation at a 95% confidence level was calculated as R-2 = 0.703. The main and interaction effects of the process parameters on the acceleration amplitude were evaluated, and the percentage contributions of the process parameters to the acceleration amplitude were determined by variance analysis. In addition, scanning electron microscope (SEM) and optical microscope images of the drill wear were taken, and the wear characteristics and acceleration amplitude were correlated. The most effective parameters on acceleration amplitude were determined as the number of holes drilled, workpiece hardness, cutting speed, and feed rate. No significant effect of drill length/tool overhang was observed. With increasing cutting speed, number of holes drilled and the drill length/tool overhang, the acceleration amplitude values increased, although they decreased with increasing workpiece hardness.