Objective To examine the effect of nickel-titanium rotary instruments in reducing post-operative pain.Methods 95 molars with pulpal and/or periapical involvement were randomly assigned to two groups for root canal preparation. One group was treated with ProFile nickel-titanium rotary instruments; the other was treated by using stainless steel hand files-FlexoFile. The incidence and degree of post-operative pain after root canal preparation in the two groups were recorded.Results In ProFile group, the incidence of post-operative pain was 27.7%, while 62.5% of the teeth developed post-operative pain after hand preparation. The difference between two groups was statistically significant (P