Abstract Background Emerging research indicates the potential for early transition from intravenous to oral antimicrobial therapy in certain infections. This trend may have implications for outpatient parenteral antibiotic therapy (OPAT) programs, as the demand for prolonged intravenous treatment could decrease. The objective of this study was to evaluate the frequency and evolution of OPAT courses of ≥ 14 days over the years and determine the medical justification for those prolonged treatments. Methods All patients treated intravenously for ≥ 14 days by the OPAT program at Lausanne University Hospital, Switzerland, between 2017 and 2022 were included in the study. Data were extracted from a prospectively established OPAT database. Prevalence of prolonged antibiotic treatment and its clinical and microbiological information were identified. Results During the study period, a total of 2,448 treatment courses were administered: 1,636 intravenous (IV) and 812 oral treatments. Of the IV treatments courses, 749 (36%) were of a duration of ≥ 14 days, without discernible trend over the 6-year study period. The most common type of infections needing prolonged treatment were bone and joint infections (31%), endovascular infections (18%), complicated intra-abdominal infections (15%), and urinary tract infections (11%), with only minor fluctuations in these proportions during the study period. Finally, the use of second-line antibiotics (piperacillin-tazobactam, carbapenems and vancomycin) did not increase over the years, suggesting that prolonged intravenous antibiotic therapy is not linked to an increase of anti-microbial resistance in our cohort. Conclusions Despite the general trend towards shorter intravenous treatment courses in infectious diseases, our OPAT unit did not observe a decline in the use of prolonged intravenous antibiotic therapy between 2017 and 2022, suggesting that OPAT units will probably not see a decrease in their activities in the near future.