AIM: To evaluate the effect of reciprocating amplitude and progressive angular increment on fatigue life enhancement of NiTi rotary endodontic instruments. METHODOLOGY: ProTaper F2 instruments were operated in steel artificial canals with both stationary reciprocating (SR) and progressive reciprocating (PR) motions. The SR motions involved symmetric to and fro reciprocation of ± 180(o) , ± 135(o) , ± 90(o) , ± 60(o) and ± 45(o) . The PR motions were ± 45(o) stationary motion superimposed with angular increments of 7(o) , 11(o) , 22.5(o) or 31(o) whenever an instrument completed 1, 10 or 30 reciprocating cycles (rc). The fatigue lives were compared with those under continuous rotation (CR) and a reciprocating operation with a forward 144(o) and backward 72(o) motion proposed by Yared (2008). The statistical significance of these operating modes on fatigue life was examined using one way anova and post hoc Tukey's tests at P = 0.05. Fractographic analysis was also applied to probe the fracture mechanisms of different rotation motions. RESULTS: Fatigue life increased with decreasing reciprocating amplitude. Operating in the SR increased fatigue life by 355% over that in the CR. Except for the 22.5(o) increment, all PR motions yielded longer fatigue lives than the SR motion. A progressive reciprocating operation with a ± 45(o) reciprocating amplitude and a + 7(o) progressive angular increment every 10 reciprocating cycles (± 45(o) /10rc/+7(o) ) increased fatigue life by 990% over that in the CR motion. In terms of life enhancement over the CR motion, the larger the curvature the less are the differences between different movements. Single crack initiation sites were found in the CR and SR motions, while three crack initiation sites were typical in the ± 45(o) /10rc/+7(o) motion. CONCLUSIONS: Fatigue life increased with decreasing reciprocating amplitude in stationary reciprocation. A progressive reciprocating operation with ± 45(o) /10rc/+7(o) motion led to significant fatigue life enhancement and multiple fatigue crack initiation in NiTi endodontic instruments.