Purpose <p>Bone and joint infections (BJIs) cause significant morbidity, and current guidelines suggest treatment with parenteral antibiotics for 4–6 weeks. However, utility of oral antibiotics as a potential alternative has yet to be thoroughly investigated. To provide a statistical appraisal of literature comparing treatment success and complication rates of oral antibiotics to parenteral antibiotics for BJIs.</p> Methods <p>PubMed, Embase, Cochrane, and Web of Science databases were queried for studies published by November 12, 2024. Randomized controlled trials (RCTs) comparing parenteral to oral regimens for the entire treatment duration were included, as well as comparative studies evaluating “early switch” therapy, defined as switching from parenteral to oral antibiotics within 28 days. Data was pooled and sub-analyzed according to design (RCTs or early switch cohorts). Treatment successes and complications for parenteral and oral groups were assessed via DerSimonian-Laird binary random-effects modeling with a <i>p</i>-value &lt; 0.05 indicating significance.</p> Results <p>Six RCTs (1,310 patients) compared treatment success of parenteral or oral regimens for the duration of the infection treatment, and six retrospective cohort studies (1,106 patients) compared parenteral therapy to early switch therapy. Meta-analysis of RCTs demonstrated no significant difference for treatment success rates for oral versus parenteral antibiotics (OR 1.09 [0.79–1.51], <i>p</i> = 0.93, <i>I</i>^<i>2</i> = 0.00%). Six early switch cohort studies demonstrated that oral antibiotics had significantly higher success (OR = 1.70 [1.13–2.54], <i>p</i> = 0.01, <i>I</i>^<i>2</i> = 0.00%). Meta-data of both RCTs and early switch cohort studies demonstrated no significant difference in complication rates.</p> Conclusion <p>No difference in treatment success rates or complication rates was found when comparing oral and parenteral antibiotics. Oral antibiotics are a possible option for treatment of BJIs.</p>