Objectives To evaluate the effectiveness of passive ultrasonic irrigation (PUI) compared with non-activated irrigation (NAI) on periapical healing and root canal disinfection.Data source A comprehensive search without restrictions was performed in the following systematic electronic databases: PubMed, Scopus, Cochrane, Web of Science, ScienceDirect and OpenGrey. Additional studies were sought through hand-searching in the main endodontic journals.Data selection We included clinical trials that compared PUI and NAI clinical success and root canal disinfection outcomes. The risk of bias was assessed based on the Cochrane Collaboration common scheme for bias assessment. The power analysis of each study was calculated based on the disinfection rates and sample size, and the evidence was qualified using the GRADE tool.Data synthesis A total of 346 non-duplicated studies were retrieved in the systematic search. One study that assessed the clinical success rate through periapical radiographic healing evaluation and two studies that evaluated root canal disinfection through bacterial growth were considered eligible. These three studies were classified as low risk of bias. The study evaluating radiographic treatment outcome showed no statistical difference (P >0.05). The studies demonstrated large variability among methodology and, in general, low power and moderate evidence. Inconclusive results were reported regarding root canal disinfection when comparing PUI to NAI strategies.Conclusions Based on the findings, there was no evidence of effectiveness improvement on periapical healing and bacterial disinfection that supports the use of PUI over the NAI in clinical practice.