Objective: Unstable shoe has been recommended as a safety factor for healthy individuals and as a tool for osteoarthritis patients in order to reduce the pain. The aim of this study was to investigate the effect of unstable shoe on biomechanical variables related to injury during running.Materials & Methods: Twenty five healthy young available males (21±2.27 years) participated in this quasi-experimental study. The subjects were asked to run on the force plate barefoot, with unstable shoe and with control shoe. variables of active and passive joint power, peak anterior-posterior forces, active and passive vertical force, loading rate and impulse of posterior and passive vertical forces were recorded using synchronizing force plate and video camera were registered and were calculated in MATLAB software. A repeated measure of ANOVA was used to test the hypothesis in SPSS software (version 20, p<0.05).Results: Negative power at Ankle joint decreased significantly by 49%, 35% respectively using unstable shoe compared to control shoe and barefoot conditions (P=0.02, P<0.05). Furthermore, unstable shoe decreased the active ankle power significantly compared to barefoot condition by 23% (P=0.01). Loading rate and peak of passive vertical force, impulse and peak of posterior force increased significantly in unstable shoe compared to control shoe (P<0.05).Conclusion: Unstable shoe increased some of running related injuries risk factors such as loading rate and peak of passive vertical force, impulse and peak of posterior force. Furthermore, this shoe could decrease absorption potential shank muscles and ankle active stability compared to the control shoe. However, with increase of ankle active power compared to barefoot and lower anterior force, unstable shoe could improve the ankle joint force generation and propulsion potential.