Introduction Mural infective endocarditis (MIE) is a rare type of endovascular infection. We present a comprehensive series of patients with mural endocarditis. Methods Patients with infectious endocarditis (IE) from 35 Spanish hospitals were prospectively included in the GAMES registry between 2008 and 2017. MIEs were compared to non-MIEs. We also performed a literature search for cases of MIE published between 1979 and 2019 and compared them to the GAMEs series. Results Twenty-seven MIEs out of 3676 IEs were included. When compared to valvular IE (VIE) or device-associated IE (DIE), patients with MIE were younger (median age 59 years, p  < 0.01). Transplantation (18.5% versus 1.6% VIE and 2% DIE, p  < 0.01), hemodialysis (18.5% versus 4.3% VIE and 4.4% DIE, p  = 0.006), catheter source (59.3% versus 9.7% VIE and 8.8% DIE, p  < 0.01) and Candida etiology (22.2% versus 2% DIE and 1.2% VIE, p  < 0.01) were more common in MIE, whereas the Charlson Index was lower (4 versus 5 in non-MIE, p  = 0.006). Mortality was similar. MIE from the literature shared many characteristics with MIE from GAMES, although patients were younger (45 years vs. 56 years, p  < 0.001), the Charlson Index was lower (1.3 vs. 4.3, p  = 0.0001), catheter source was less common (13.9% vs. 59.3%) and there were more IVDUs (25% vs. 3.7%). S. aureus was the most frequent microorganism (50%, p  = 0.035). Systemic complications were more common but mortality was similar. Conclusion MIE is a rare entity. It is often a complication of catheter use, particularly in immunocompromised and hemodialysis patients. Fungal etiology is common. Mortality is similar to other IEs.