The aim of the present study was to evaluate and compare postoperative pain after foraminal instrumentation using 5.25% sodium hypochlorite (NaOCl) or 2% chlorhexidine (CHX) gel irrigation protocol in nonvital single-rooted teeth after reciprocating instrumentation. Sixty-two volunteers presenting a single root canal diagnosed with asymptomatic necrosis and apical periodontitis were randomized into 2 experimental groups regarding the irrigation protocol (ie, 5.25% NaOCl and 2% CHX gel groups). Endodontic treatment was performed in a single session under reciprocating instrumentation with foraminal instrumentation. Volunteers were instructed to record pain intensity. Scores from 1 to 4 were attributed to each kind of pain after 24, 48, and 72 h. Kolmogorov-Smirnov and Student´s t tests were used to determine significant differences at p<0.05. On average, the percentage of patients that had no or mild pain after 24, 48 or 72 h was 77.4%, 88.7% and 95.1%, respectively. No statistically significant age difference was found between the groups (p>0.05, Student´s t test). Postoperative pain showed no statistically significant difference at any observation period when using 5.25% NaOCl or 2% CHX gel (p>0.05). Moreover, no significant difference was observed in the mean number of analgesic tablets used between the groups (p>0.05). In conclusion, the use of 5.25% NaOCl or 2% CHX gel resulted in the same postoperative pain. Therefore, it can be inferred that irrigant choice has no relation with short-term follow up regarding postoperative pain.