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Background and Importance Linezolid-induced thrombocytopenia is a clinically relevant adverse reaction in hospitalised patients, particularly during prolonged treatment. It often necessitates treatment modification or discontinuation by hospital pharmacy services. Given the platelet lifespan (7–10 days), understanding the temporal relationship between linezolid exposure and platelet decline is crucial for effective monitoring and management.Aim and Objectives To determine the incidence of thrombocytopenia (<150 × 10 9/L) in patients treated with linezolid and to identify associated risk factors.Material and Methods A retrospective, observational study was conducted in a tertiary hospital from October 2024 to February 2025.Hospitalised adults who received linezolid for ≥48 hours were included. Data collected included demographic, clinical, and laboratory variables: baseline and final platelet counts, serum creatinine, treatment duration, clinical indication, isolated microorganisms, and plasma linezolid levels (when available). Patients with pre-existing thrombocytopenia were excluded. Statistical analysis was performed using the Wilcoxon paired test.Results Of 314 patients identified, 164 met the inclusion criteria (mean age 75 years; 52% women). Eighteen patients (11%) developed thrombocytopenia during therapy. Mean treatment duration was 10 days (standard deviation 3.4).Renal function worsened in 61% of thrombocytopenic patients, with a mean 9% increase in serum creatinine (final mean creatinine 0.7 mg/dL). No patients with thrombocytopenia had plasma linezolid concentrations measured. A significant reduction in platelet count was observed at the end of treatment (p < 0.001). The main prescribing departments were Pneumology (33%), Traumatology (22%), Internal Medicine (17%), Solid Organ Transplantation (11%), and others (17%).Conclusion and Relevance Linezolid-associated thrombocytopenia occurred in approximately 11% of treated patients, mainly among those with renal impairment. Although incidence was moderate, regular platelet monitoring and individualised renal assessment are recommended, especially in prolonged or high-risk treatments. Determining plasma linezolid concentrations in selected patients could enhance treatment safety and optimise therapeutic outcomes.Conflict of Interest No conflict of interest