The fracture of nickel-titanium rotary instruments is a serious problem that can jeopardise the outcome of root canal treatment. The aim of this study was to compare the cyclic fatigue resistance of new and used Mtwo rotary nickel-titanium instruments in artificial canals with two different radii of curvature. Four hundred and twenty Mtwo instruments were used in the present study. Thirty new and 30 used instruments of each size were tested for cyclic fatigue in artificial canals with radii of curvature of 5 or 10 mm. Each instrument was rotated until fracture occurred and the number of cycles to fracture was calculated by multiplying time to fracture and rotational speed. Data were analysed using a t-test. According to the results of the study, radius of curvature was an important factor on cyclic fatigue resistance and clinical use significantly reduced the instrument lifespan.