This study was conducted to evaluate postoperative pain after root canal preparation with ProTaper Next and WaveOne NiTi Systems. Fifty two patients with mandibular permanent premolars and molars, showing signs/symptoms of symptomatic irreversible pulpitis were selected from the outpatient clinic of endodontic department, Cairo University. An approval from the ethic committee and an informed consent from the patients were taken. Patients were randomly divided into two groups; Comparator Group: Root canal instrumented with WaveOne instruments (n=26), and Intervention Group: Root canal instrumented with Protaper Next (PTN) instruments (n=26). Postoperative pain was recorded using numerical rating scale (NRS) at 6, 12, 24, 48 hours intervals. Results showed that a significantly lower levels of postoperative pain in the PTN group compared to WaveOne group at 6 and12 hours. No significant difference was found between both groups at 24 and 48 hours. In conclusion, PTN rotary system was able to minimize the risk of postoperative pain intensity, as compared to WaveOne reciprocating system in the first 24 hour.