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Background and Importance The Paediatric Antimicrobial Stewardship Program promotes rational antifungal use and monitoring of antifungals.Aim and Objectives To describe the experience with pharmacokinetic monitoring of posaconazole suspension in immunocompromised paediatric patients, and to evaluate its effectiveness and safety.Material and Methods A retrospective study was conducted in a tertiary hospital (January 2017–December 2023). Immunocompromised patients under 18-years-old receiving posaconazole suspension prophylaxis with at least one plasma concentration (Cp) determination were included. Initial dosing was posaconazole 4 mg/kg/8h if <34 kg, or 200 mg/8h if >34 kg; in chronic granulomatous disease, dosing was every 12h. Therapeutic range considered was 0.7–2.5 µg/ml. To ensure steady-state, measurements were obtained at least 7 days after treatment initiation.Demographic, clinical, and pharmacological variables were collected. Quantitative variables were expressed as median ± interquartile range (IQR), and qualitative variables as number (%). Statistical analysis was performed using SAS software.Results Seventy-one patients were included (67.6% male), with a median age of 4.8 (IQR 2.4–8.9) years. Main underlying conditions were primary immunodeficiencies (23/71, 32.4%), bone marrow failure/myelodysplastic syndrome (15/71, 21.1%), acute lymphoblastic leukaemia (14/71, 19.7%), and acute myeloid leukaemia (8/71, 11.3%).In total, 373 Cp were collected: 178 (47.8%) were therapeutic, 187 (50.1%) subtherapeutic, eight (2.1%) supratherapeutic. Median daily dose was 13.4 (IQR 12–18.4) mg/kg/day; prophylaxis duration was 209 (IQR 91–444) days. No significant correlation was observed between dose and Cp (r=-0.9584), and no significant differences in dose were found between therapeutic and supratherapeutic Cp (p=0.0614).Six (8.5%) patients developed breakthrough invasive fungal infections (IFI): three proven, three probable. Median time to IFI was 78.6 (IQR 51–140) days, 11/16 (68.7%) Cp were subtherapeutic. Among patients without IFI, 176/357 (49.2%) Cp were subtherapeutic. Despite the higher proportion of subtherapeutic Cp, the difference was not statistically significant (p=0.128). Prophylaxis was discontinued in four (5.6%) patients due to suspected adverse events: transaminase elevation, gastrointestinal disorders, and skin reactions.Conclusion and Relevance Pharmacokinetic monitoring of posaconazole suspension in immunocompromised paediatric patients is essential and necessary to optimise antifungal prophylaxis. The standard prophylactic dose of posaconazole may be insufficient to achieve therapeutic Cp, as evidenced by the high percentage of subtherapeutic Cp. Overall, posaconazole was well tolerated in most patients.Conflict of Interest No conflict of interest