Background: As Q fever, caused by Coxiella burnetii, is a major health challenge due to its cardiovascular complications, we aimed to detect acute Q fever valvular injury to improve therapeutic management. Methods: In the French national reference center for Q fever, we prospectively collected data from patients with acute Q fever and valvular injury. We identified a new clinical entity, acute Q fever endocarditis, defined as valvular lesion potentially caused by C. burnetii: vegetation, valvular nodular thickening, rupture of chorda tendinae, and valve or chorda tendinae thickness. To determine whether or not the disease was superimposed on an underlying valvulopathy, patients' physicians were contacted. Aortic bicuspidy, valvular stenosis, and insufficiency were considered as underlying valvulopathies. Results: Of the 2434 patients treated in our center, 1797 had acute Q fever and 48 had acute Q fever endocarditis. In 35 cases (72%), transthoracic echocardiography (TTE) identified a valvular lesion of acute Q fever endocarditis without underlying valvulopathy. Positive anticardiolipin antibodies (>22 immunoglobulin G-type phospholipid units [GPLU]) were independently associated with acute Q fever endocarditis (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.3-5.5]; P = .004). Acute Q fever endocarditis (OR, 5.2 [95% CI, 2.6-10.5]; P < .001) and age (OR, 1.7 [95% CI, 1.1-1.9]; P = .02) were independent predictors of progression toward persistent C. burnetii endocarditis. Conclusions: Systematic TTE in acute Q fever patients offers a unique opportunity for early diagnosis of acute Q fever endocarditis and for the prevention of persistent endocarditis. Transesophageal echocardiography should be proposed in men, aged >40 years, with anticardiolipin antibodies >60 GPLU when TTE is inconclusive or negative.