OBJECTIVE The objective of this systematic review and meta-analysis (SRM) was to answer the question as to whether the use of ultrasonic irrigation (UI) results in better antimicrobial activity in root canal disinfection compared to conventional irrigation (CI). METHODS A literature search was performed in the main scientific databases, carried out until October 2021. The eligibility criteria were randomized clinical trials (RCTs). Two meta-analyses were conducted using R software with the "META" package. The mean difference (MD) and odds ratio (OR) measure of effect were calculated. The fixed effect model was applied with a 95% confidence interval. The Cochrane collaboration scale was used to assess risk of bias and the GRADE tool to assess the quality of evidence. RESULTS A total of 1782 records were screened, and 12 studies meeting the criteria were included in this review. A low risk of bias was observed for most domains, except allocation concealment that was considered unclear. The certainty of evidence was classified as moderate in the OR meta-analyses and low in the MD meta-analyses. Ultrasonic irrigation resulted in a better antimicrobial effect in both meta-analyses, MD 1.42 [1.60; 1.23] p < 0.0001, I2 = 80%; and OR 3.86 [1.98; 7.53] p< 0.0001, I2 = 28.7%. CONCLUSIONS Within the limitations of this SRM, UI presented better antimicrobial efficacy than CI. CONCLUSIONS UI should be used by clinicians as it promotes better antimicrobial efficacy in patients undergoing endodontic treatment.