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Aims: This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. Methods:A literature search for clinical trials was made on the PUBMED (Medline), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was carried out according to the CONSORT statement. Results:One clinical trial and four randomized clinical trials (RCTs) were selected from the 172 papers initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine to reduce microorganisms in one study and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in one study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. Conclusions:The available evidence on this topic is scarce and the findings of studies were not consistent. Additional RCTs using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed.