Background Itraconazole is the oral antifungal agent of choice for the treatment of histoplasmosis. Rarely, it can cause cardiovascular adverse effects, including hypokalemia, congestive heart failure, edema, and hypertension. Methods We reviewed the medical records of 12 patients who had been on courses of itraconazole between April 20, 2016, and April 19, 2017. By reviewing blood pressure measurements, medications, and symptoms on clinic visits, we were able to ascertain temporal changes related to the initiation of itraconazole. Results We report a case series of 5 patients who developed new or worsening hypertension while treated with itraconazole. Conclusions Our rate of hypertension was higher than anticipated compared with the package insert rate of 2% to 3%. Given the frequent necessity of prolonged itraconazole treatment and its suspected pathophysiology, prescribers should be aware of itraconazole's cardiovascular effects and should consider investigation into antimineralocorticoid therapies (eg, spironolactone) to limit its adverse effects.