Safar was born in Vienna, Austria, in 1924 into a medical family. His father, Karl, was an ophthalmologist and his mother, Vinca (Landauer), who had a Jewish grandmother, was a pediatrician. He graduated from the University of Vienna in 1948. He married Eva Kyzivat and moved from Vienna to Hartford, Connecticut, in 1949 for surgical training at Yale University. He completed training in anesthesiology at the University of Pennsylvania in 1952. That same year he worked in Lima, Peru, and founded that country’s first academic anesthesiology department. In 1954, he became chief of the department of anesthesiology at Baltimore City Hospital.
Together with James Elam, he rediscovered the initial steps in CPR. These included the head tilt and chin lift maneuver to open the airway of an unconscious victim, as well as the mouth-to-mouth breathing. He influenced Norwegian doll maker Asmund Laerdal of Laerdal company to design and manufacture mannequins for CPR training called Resusci Anne. Safar, who began to work on CPR in 1956 at Baltimore City Hospital, demonstrated in a series of experiments on paralyzed human volunteers that rescuer exhaled-air mouth-to-mouth breathing could maintain satisfactory oxygen levels in the non-spontaneously breathing victim, and showed that even laypeople could effectively perform mouth-to-mouth breathing to save lives. He combined the A (Airway) and B (Breathing) components of CPR with the C (chest compressions). He wrote the book ABC of Resuscitation in 1957, which established the basis for mass training of CPR. This A-B-C system for CPR training of the public was later adopted by the American Heart Association, which promulgated standards for CPR in 1973.