Objective: The purpose of this study was to compare the effect of nano-silver (Nanotech Egypt for photo Electronics, Cairo, Egypt) irrigating solution versus sodium hypochlorite on postoperative pain after single-visit endodontic therapy. Methods: A randomized controlled clinical trial was designed and carried out in the endodontic department at Cairo University. Fifty healthy patients with asymptomatic necrotic teeth that were scheduled for non-surgical root canal treatment were enrolled. Single-visit root canal treatment was performed using ProTaper Universal (PTU; Dentsply Maillefer, Ballaigues, Switzerland) rotary files and for irrigation NaOCl 5.25% (Egyptian Company for household products under license of Clorox. Co. Cairo, Egypt) (control group, n=25) and nano-silver irrigating solution (intervention group, n=25) were used. After obturation, post-operative pain was assessed using a visual analogue scale (VAS) after 4, 24, and 48 hours. Chi-square test was used to compare VAS values between tested groups within each follow-up period and Wilcoxon signed rank test was used for within group comparisons over time. Results: Insignificant differences between NaOCl group and nano-silver group were found in pain scores for each follow-up period. The pain score decreased significantly after 24 hours (p=0.003) and after 48 hours (p=0.001) in intervention group. Control group showed similar results were the pain score decreased significantly after 24 hours (p=0.008) and after 48 hours (p=0.001). Conclusion: Both tested irrigants were associated with a decrease of postoperative pain over time, in patients undergoing single-visit endodontic treatment with necrotic pulps. There was no statistical significant difference between both groups.