In 2019, our center introduced routine oral rivaroxaban prophylaxis (10 mg once daily) for all patients with ACTH-dependent CS.<h4>Objective</h4>To evaluate the safety and effectiveness of routine rivaroxaban prophylaxis in ACTH-dependent CS.<h4>Methods</h4>We retrospectively reviewed 70 adults with ACTH-dependent CS managed between 2012 and 2025 (29 pre-2019 and 41 post-2019) to compare VTE incidence before and after the introduction of rivaroxaban.<h4>Results</h4>There were no differences in baseline characteristics between the 2 groups. Here, POMC is linked to substance dependence.