Posaconazole tablets are well tolerated and efficacious in the prophylaxis and treatment of aspergillosis, mucormycosis, and other invasive fungal infections. There have been case reports of posaconazole-induced pseudohyperaldosteronism, however, its occurrence and association with serum posaconazole drug levels has not previously been investigated.In this single-center retrospective observational study, we examined the occurrence of posaconazole-induced pseudohyperaldosteronism (PIPH) in outpatients newly starting posaconazole and evaluated differences in serum posaconazole concentrations and clinical characteristics between those with and without this syndrome.Sixty-nine patients receiving posaconazole were included, of whom 16 (23.2%) met the definition of PIPH. Patients with PIPH were significantly older (61.1 vs 44.7 years, P=0.007) and more frequently had hypertension prior to starting posaconazole (68.8% vs 32.1%, P=0.009). Patients with PIPH had a significantly higher median serum posaconazole level than those without PIPH (3.0 vs 1.2 µg/mL, P <=0.0001). There was a positive correlation between serum posaconazole levels and changes in systolic blood pressure (r =.37, P=0.01), a negative correlation between serum posaconazole levels and changes in serum potassium (r =-.39, P=0.006), and a positive correlation between serum posaconazole levels and serum 11-deoxycortisol (r =.69, P<0.0001).Posaconazole is associated with secondary hypertension and hypokalemia, consistent with pseudohyperaldosteronism, and development is associated with higher serum posaconazole concentrations, older age, and baseline hypertension.