ObjectivesThe aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. MethodsThis was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. ResultsIn total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75–59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan–Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1–2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09–2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5–3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). ConclusionsSAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.