There are many limitations to the current antibiotics used for the treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Ceftaroline is a new fifth-generation cephalosporin approved for the treatment of skin and soft tissue infections caused by MRSA and community-acquired pneumonia. We propose that ceftaroline can also be used successfully in more severe MRSA infections, including endocarditis. We conducted a retrospective chart review in a university-affiliated Department of Veterans Affairs hospital in San Diego, California (USA) of ten inpatients treated with ceftaroline for severe MRSA infection, including five cases of probable endocarditis (including two endocardial pacemaker infections), one case of pyomyositis with possible endocarditis, two cases of pneumonia (including one case of empyema), two cases of septic arthritis (including one case of prosthetic joint infection), and two cases of osteomyelitis. Seven of the 10 patients achieved microbiological cure. Six of the 10 patients achieved clinical cure. Seven patients were discharged from the hospital. Three patients were placed on comfort care and expired in the hospital; one achieved microbiological cure before death, and two remained bacteremic at time of death. In most patients, ceftaroline was effective for treatment of MRSA bacteremia and other severe MRSA infections. Adverse effects seen included rash, eosinophilia, pruritus, and Clostridium difficile infection. Ceftaroline can be a safe and effective drug for treatment of severe MRSA infections, and further comparative studies are warranted.