Abstract Background Since June 2017, oral pre-exposure prophylaxis (PrEP) has been reimbursed in Belgium for people at substantial risk of HIV. To inform the national PrEP programme, we described sociodemographic characteristics of PrEP users, PrEP dispensing practices, testing for HIV and sexually transmitted infections (STIs; gonorrhoea, chlamydia and syphilis), and incidence of HIV and STIs. Methods Analysis of routinely collected social health insurance claims data from all individuals who were dispensed at least one PrEP prescription between June 2017 and December 2019. Using logistic regression adjusted for age, we examined associations between sociodemographic characteristics and having been dispensed PrEP only once in the first six months of PrEP use. Results Overall, 4559 individuals were dispensed PrEP. Almost all PrEP users were male (99.2%, 4522/4559), with a median age of 37 years (IQR 30–45). A minority were entitled to an increased healthcare allowance (11.4%, 514/4559). 18% (657/3636) were dispensed PrEP only once in the first six months of PrEP use. PrEP users younger than 25 years, unemployed, entitled to an increased healthcare allowance, and who initiated PrEP between January 2019 and June 2019 were more likely to have had no PrEP dispensing after initiation compared to their counterparts. The testing rates for bacterial STIs and HIV were 4.2 tests per person-year (95% CI 4.1–4.2) and 3.6 tests per person-year (95% CI 3.5–3.6), respectively. Twelve individuals were identified to have seroconverted during the study period, resulting in an HIV incidence rate of 0.21/100 person-years (95% CI 0.12–0.36). The incidence of bacterial STIs was 81.2/100 person-years (95% CI 78.7–83.8). Conclusions The study highlights challenges in PrEP persistence and a high incidence of bacterial STIs among individuals receiving PrEP. Tailored prevention support is crucial for individuals with ongoing HIV risk to optimise PrEP effectiveness. Integrated STI testing and prevention interventions within PrEP care are ...