An increase in demand on solid wood that is insufficient supply to meet in the world necessarily directed to other engineering materials that could be an alternative to the solid wood. In this context, instead of using solid wood in furniture and construction industry, wood-based panels such as medium density fiberboard (MDF) and particleboard (PB) have become widely used as construction material. Limited research has been done in the field of fastener performance as mechanical properties with different parameters in the joints constructed with these panels. Therefore, in this study, the parameters of screw type, pilot hole, screw orientation, water treatment and adhesives were investigated in MDF and PB. The results indicated that the highest direct screw withdrawal (DSW) resistance was observed in the test blocks applied with PU and the lowest DSW resistance was in the test blocks without a pilot hole drilled in both materials. In addition, MDF in general had better DSW resistance than PB in almost all combinations of the parameters. The treatment of water into MDF and PB test blocks negatively affects the DSW resistance. The DSW resistance in the face orientation was found to be higher than the corresponding ones in the side orientation in both materials.