Aim To compare static cyclic fatigue resistance of unused, unused and sterilized and clinically used conventional NiTi GT and M-Wire GTX files. Methodology One hundred and sixty new files (80 GT and 80 GT series X) were divided into four control groups and four experimental groups (n= 20 each). Control groups were new unused files, and new sterilized files. In the experimental groups instruments were used in 3 (GT1 and GTX1 groups) or 4 molars (GT2 and GTX2 groups). Cyclic fatigue resistance was tested in stainless steel curved canals (60°, r = 3mm). Each file was rotated until fracture (300 rpm, 2 N·cm torque). Time to fracture (s) was registered. Mean life, eta and beta parameters of their Weibull distributions were calculated. Results Unused and sterilized GTX files will last significantly longer than GT files with a probability of 75% and 65% respectively, while mean life was significantly longer for GT than for GTX in used files with a probability of 68%. Sterilized GT files will last longer than unused files with a probability of 66%. In both brands, unused and sterilized files will last significantly longer than files used clinically with a probability higher than 98%.The probability that GT will last longer after being used in three rather than four molars was 62% (statistically significant), and 52% (not statistically significant) for GTX. Conclusions GTX files had an extended cyclic fatigue life when compared with GT when they were unused or unused and sterilized, but GT were significantly more resistant to cyclic fatigue after clinical usage than GT series X files 3 mm from the tip. Sterilization of files enhanced the cyclic fatigue resistance of GT instruments. Clinical use of files diminished cyclic fatigue resistance. This article is protected by copyright. All rights reserved.