Peripheral mycotic aneurysms (PMAs) are a relatively rare but serious complication of infective endocarditis (IE). We conducted the current study to describe and compare the current epidemiologic, microbiologic, clinical, diagnostic, therapeutic, and prognostic characteristics of patients with symptomatic PMAs (SPMAs). A descriptive, comparative, retrospective observational study was performed in 3 tertiary hospitals, which are reference centers for cardiac surgery. From 922 definite IE episodes collected from 1996 to 2011, 18 patients (1.9%) had SPMAs. Because all SPMAs developed in left-sided IE, we performed a comparative study between 719 episodes of left-sided IE without SPMAs and 18 episodes with SPMAs. We found a higher frequency of intravenous drug abuse, native valve IE, intracranial bleeding, septic emboli, multiple embolisms, and IE diagnostic delay >30 days in patients with SPMAs than in patients without SPMAs. The causal microorganisms were gram-positive cocci (n =10), gram-negative bacilli (n = 2), gram-positive bacilli (n = 3), Bartonella henselae (n = 1), Candida albicans (n = 1), and negative culture (n = 1). The median IE diagnosis delay was 15 days (interquartile range [IQR], 13-33 d) in the case of high-virulence microorganisms versus 45 days (IQR, 30-240 d) in the case of low- to medium-virulence microorganisms. Twelve SPMAs were intracranial and 6 were extracranial. In 10 cases (8 intracranial and 2 extracranial), SPMAs were the initial presentation of IE; the remaining cases developed symptoms during or after finishing parenteral antibiotic treatment. The initial diagnosis of intracranial SPMAs was made by computed tomography (CT) or magnetic resonance imaging in 6 unruptured aneurysms and by angiography in 6 ruptured aneurysms. The initial test in extracranial SPMAs was Doppler ultrasonography in limbs, CT in liver, and coronary angiography in heart. Four (3 intracranial, 1 extracranial) of 7 (6 intracranial, 1 extracranial) patients treated only with antibiotics died. Surgical resection was performed in 7 (3 intracranial, 4 extracranial) and endovascular repair in 4 (3 intracranial, 1 extracranial) patients; all of them survived. In conclusion, we found that SPMAs were a rare complication of IE that developed only in left-sided IE, and especially in native valves. Intracranial hemorrhage, embolism, multiple embolisms, and diagnostic delay of IE were more common in patients with SPMAs. The microbiologic profile was diverse, but microorganisms of low-medium virulence were predominant, and had a greater delayed diagnosis of IE than those caused by microorganisms of high virulence. SPMAs were often the initial presentation of IE. The most common location of SPMAs was intracranial. Noninvasive radiologic imaging techniques were the initial imaging test in intracranial unruptured SPMAs and in most extracranial SPMAs. Surgical and endovascular treatments were safe and effective. Endovascular treatment could be the first line of treatment in selected cases. Mortality was high in those cases treated only with antibiotics.