AimThis randomized, prospective, double‐blind, clinical trial assessed the effect of 1.3% and 5.25% sodium hypochlorite (NaOCl) as irrigants on post‐endodontic pain and medication intake following root canal treatment of mandibular molars with nonvital pulps.MethodologyThree hundred and eight patients, each with one symptomatic or asymptomatic molar, were randomly assigned, using the permuted‐block method, into two equal groups according to NaOCl concentration: 1.3% or 5.25% (n = 154). For both groups, syringe irrigation was performed using a 27‐gauge needle advanced into the canal to a depth of 3 mm from the working length; 3 mL were used between every two consecutive instruments. All root canal treatments were carried out in two visits, with no intracanal medication, by trained postgraduate students. The canals were prepared using the ProTaper Universal rotary system during the first visit. In the second visit 7 days later, the same irrigant per group was used and the canal walls were reprepared with the final instrument before filling the canal using the modified single‐cone technique with an epoxy resin‐based sealer. Patients assessed their postoperative pain using a 0–10 numerical rating scale immediately after instrumentation, 3, 24, 48 h and 7 days after the first visit and immediately following root canal filling. The incidence of rescue medication intake (Sham or analgesic) was also recorded; patients received a sham capsule to be used first, but, if pain persisted, an analgesic was prescribed. Outcome data were analysed using Mann–Whitney U‐test, Friedman's test, Wilcoxon's rank test and chi‐square (χ2) test. Relative risk reduction (RRR) and its 95% confidence interval (CI) were calculated for binary data.ResultsThe incidence and intensity of postoperative pain were significantly lower with 1.3% NaOCl than 5.25% NaOCl at all time‐points (P < 0.05). Postoperative pain intensity exceeded preoperative pain at 3 and 24 h with 5.25% NaOCl only (P < 0.05). The RRR in pain incidence was 38% (95% CI: 17%, 54%) immediately after instrumentation, 41% (95% CI: 31%, 49%) at 3 h, 42% (95% CI: 32%, 51%) at 24 h, 59% (95% CI: 45%, 69%) at 48 h, 62% (95% CI: 27%, 80%) at 7 days and 81% (95% CI: 68%, 89%) after root filling. RRR was 38% (95% CI: 1%, 61%) for sham intake and 69% (95% CI: 37%, 85%) for analgesic intake.ConclusionsUsing 1.3% NaOCl was associated with less intense and less frequent post‐endodontic pain than 5.25% NaOCl in mandibular molars with nonvital pulps treated in two visits. The incidence of pain was reduced by up to 60% within the week post‐instrumentation and 80% after root canal filling and the rescue analgesic intake by about 70% on using 1.3% NaOCl compared to 5.25% NaOCl.