Purpose: To evaluate the effect of different degrees of mesial implant inclinations on the retention and stability of two-implant mandibular overdentures retained with stud attachments. Materials and Methods: Four experimental mandibular acrylic models were constructed. Two laboratory implants were inserted in the canine areas of each model with the following degrees of mesial inclinations: 0, 5, 10, and 20 degrees. Experimental overdentures were connected to the implants with Locator extra-light retention (Le), Locator light retention (Ll), and Locator medium retention (Lm). Vertical (retention) and oblique (stability) dislodging forces (anterior, posterior, and lateral) were measured at the beginning of the study (initial retention) and after 540 cycles of denture insertion and removal (final retention). Results: The final retention was not significantly affected by small (5 degrees) and large (20 degrees) implant inclinations, but decreased with a moderate (10 degrees) inclination. For a small implant inclination (5 degrees), Lm showed the highest final retention/stability and Le showed the lowest, while for moderate and large inclinations (10 and 20 degrees), Le showed the highest final retention/stability and Lm showed the lowest. Vertical dislodging recorded the highest final stability, and lateral dislodgment recorded the lowest stability. Conclusion: Within the limitations of this in vitro study, only moderate implant angulation (10 degrees) negatively affects the final retention and stability of Locator-retained overdentures. Locator medium retention for small angulation (5 degrees) and Locator extra-light retention for moderate (10 degrees) and large (20 degrees) angulations are recommended to maintain high retention and stability after 540 cycles of denture insertion and removal. Keywords: implant inclinations, Locator, overdenture, retention, stability