Abstract Background Literature on periprosthetic joint infection (PJI) contains varying strategies and definitions of suppressive antimicrobial therapy (SAT). This study aimed to describe current SAT strategies, evaluate their clinical outcomes, and establish a consensus definition of SAT for research and clinical purposes. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was performed by searching PubMed and EMBASE from their inception to 10 March 2025. All trials and observational studies including ≥10 patients with PJI treated with SAT were eligible. Data on study, patient, and treatment characteristics, definitions, and outcomes were extracted. Study quality was appraised using the Methodological Index for Non-Randomized Studies tool. A random effects model was used to pool success rates. Definitions were developed through a modified Delphi process. Results Forty-two studies (N = 2524 patients) were included: 25 from the United States and 17 from Europe. In US literature, SAT was predominantly prescribed for acute PJI managed with debridement, antibiotics, and implant retention (DAIR), whereas European studies primarily involved PJI managed without curative intent. The pooled reported success rate of SAT was 74% (95% confidence interval [CI], 63%–85%) for acute PJI treated with DAIR and 70% (95% CI, 63%–78%) for chronic PJI treated with DAIR or without surgery. Definitions of SAT were inconsistently reported. Consensus was achieved, resulting in definitions distinguishing SAT from extended antimicrobial therapy (EAT). Conclusions Suppressive antimicrobial therapy is inconsistently defined in PJI literature with variation of practice between the United States and Europe. To harmonize research and clinical communication, we advocate the use of consensus definitions of SAT and EAT.