This study aimed to assess the resistance to cyclic fatigue of reciprocating nickel-titanium (NiTi) files (Wave One Gold and Reciproc Blue) and assess the effect of glyde and sodium hypochlorite 5.25% as a gel and liquid on it during testing. A total of 80 new WaveOne Gold primary and Reciproc Blue R25 were tested. The 40 files of the same brand were randomly assigned into four groups (n=8) and submitted to the irrigating protocol as follows: Group 1: Testing without irrigating media, Group 2: Testing with glyde, Group 3: Testing with sodium hypochlorite 5.25% gel, Group 4: Testing with sodium hypochlorite 5.25% liquid, Group 5: testing with normal saline (control). The cyclic fatigue test was performed using the appropriate preset reciprocating mode (‘RECIPROC ALL’ or ‘WAVEONE ALL’) in a specially designed endodontic motor. Resistance to fracture was determined by recording the time. The instrument tested in stainless artificial canal with 60° angle of curvature and 5 mm radius of curvature. Resistance to cyclic fatigue of the same NiTi was affected by irrigating media. Reciproc Blue R25 was associated with a higher cyclic fatigue resistance in all groups compared to WaveOne Gold Primary. The study concluded that glyde, sodium hypochlorite 5.25% as a gel and as a liquid may reduce the resistance to cyclic fatigue of WaveOne Gold and Reciproc Blue significantly. However, the type of reciprocating instrument influenced cyclic fatigue resistance with Reciproc Blue R25 being more resistant than WaveOne Gold Primary.