• The POSY-TEICO study assessed the safety of HLD teicoplanin in a real-world setting. • Incidence of nephrotoxicity with HLD of teicoplanin was determined. • Nephrotoxicity of HLD of teicoplanin was compared with historical data of vancomycin. • Nephrotoxicity was 11.0% and 6.9% in loading and maintenance dose periods, respectively. • Nephrotoxicity certainly/possibly related to teicoplanin was 12.4% in complete study period. Teicoplanin is used for treating infections caused by Gram-positive bacteria. The POSY-TEICO study assessed the safety of a high loading dose (HLD) of teicoplanin (12 mg/kg twice daily) in a real-world setting. This prospective study was conducted across six countries in Europe and enrolled adults prescribed HLD of teicoplanin between 2016 and 2019. The primary objective was to determine the incidence of nephrotoxicity following HLD of teicoplanin over loading dose period. An independent clinical adjudication committee (ICAC) assessed all study outcomes related to nephrotoxicity. The study included 300 patients (males, 68.3%), with a mean age of 63.1 years and median teicoplanin treatment duration of 16 days (interquartile range: 9–38). The number of patients with bone and joint infection, infective endocarditis, and other severe infections was 176, 36, and 80, respectively. During the loading dose period, 41 (13.8%) patients received 3 HLDs and 246 (82.8%) received ≥4 HLDs. Overall, 28 (11.0%) patients (95% CI, 7.4–15.5) experienced nephrotoxicity during loading, and 10 (6.9%) patients (95% CI, 3.4–12.4) during maintenance dose periods. The number of patients who experienced nephrotoxicity certainly or possibly related to teicoplanin according to the ICAC was 20 (7.9%; 95% CI, 4.9–11.9), 8 (5.6%; 95% CI, 2.4–10.7) and 33 (12.4%; 95% CI, 8.7–16.9) across three study periods. HLD of teicoplanin had an acceptable safety profile in patients treated for bone and joint infection, infective endocarditis, and other severe infections, and no increased risk of nephrotoxicity was observed. However, patients should be closely monitored when HLDs are administered. [ABSTRACT FROM AUTHOR]