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ABSTRACT Objectives: The aim of this study was to investigate the role of deep cryogenic treatment (DCT) on the cyclic fatigue resistance and cutting efficiency of martensitic shape memory (SM) nickel–titanium (NiTi) rotary endodontic instruments. Materials and Methods: Seventy-five HyFlex® CM instruments were randomly divided into three groups of 25 each and subjected to different DCT (–185°C) conditions based on soaking time: DCT 24 group: 24 h, DCT 6 group: 6 h, and control group. Each group was randomly subdivided for evaluation of cyclic fatigue resistance in custom-made artificial canals (n = 15) and cutting efficiency in plexiglass simulators (n = 10). The cyclic fatigue resistance was measured by calculating the number of cycles to failure (NCF) and cutting efficiency was measured using the loss of weight method. Results: Increase in NCF of instruments in DCT 24 group was highly significant (P < 0.01; Tukey's honest significant difference). There was no difference in weight loss of plexiglass simulators in all the groups (P > 0.05; one-way analysis of variance). In conclusion, deep dry cryogenic treatment with 24 h soaking time significantly increases the cyclic fatigue resistance without affecting the cutting efficiency of SM NiTi endodontic instruments.