Background: An expert panel convened by the American Dental Association Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations for the urgent management of symptomatic irreversible pulpitis with or without symptomatic apical periodontitis, pulp necrosis and symptomatic apical periodontitis, or pulp necrosis and localized acute apical abscess using antibiotics, either alone or as adjuncts to definitive, conservative dental treatment (DCDT) in immunocompetent adults. Types of Studies Reviewed: The authors conducted a search of the literature in MEDLINE, Embase, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature to retrieve evidence on benefits and harms associated with antibiotic use. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in the evidence and the Evidence-to-Decision framework. Results: The panel formulated 5 clinical recommendations and 2 good practice statements, each specific to the target conditions, for settings in which DCDT is and is not immediately available. With likely negligible benefits and potentially large harms, the panel recommended against using antibiotics in most clinical scenarios, irrespective of DCDT availability. They recommended antibiotics in patients with systemic involvement (for example, malaise or fever) due to the dental conditions or when the risk of experiencing progression to systemic involvement is high. Conclusion and Practical Implications: Evidence suggests that antibiotics for the target conditions may provide negligible benefits and probably contribute to large harms. The expert panel suggests that antibiotics for target conditions be used only when systemic involvement is present and that immediate DCDT should be prioritized in all cases.