Barnard later wrote, "For a dying man it is not a difficult decision because he knows he is at the end. If a lion chases you to the bank of a river filled with crocodiles, you will leap into the water, convinced you have a chance to swim to the other side." The donor heart came from a young woman, Denise Darvall, who had been rendered brain dead in an accident on 2 December 1967, while crossing a street in Cape Town. On examination at Groote Schuur hospital, Darvall had two serious fractures in her skull, with no electrical activity in her brain detected, and no sign of pain when ice water was poured into her ear. Coert Venter and Bertie Bosman requested permission from Darvall's father for Denise's heart to be used in the transplant attempt. The afternoon before his first transplant, Barnard dozed at his home while listening to music. When he awoke, he decided to modify Shumway and Lower's technique. Instead of cutting straight across the back of the atrial chambers of the donor heart, he would avoid damage to the septum and instead cut two small holes for the venae cavae and pulmonary veins. Prior to the transplant, rather than wait for Darvall's heart to stop beating, at his brother Marius Barnard's urging, Christiaan had injected potassium into her heart to paralyse it and render her technically dead by the whole-body standard. Twenty years later, Marius Barnard recounted, "Chris stood there for a few moments, watching, then stood back and said, 'It works.'"
Between December 1967 and November 1974 at Groote Schuur Hospital in Cape Town, South Africa, ten heart transplants were performed, as well as a heart and lung transplant in 1971. Of these ten patients, four lived longer than 18 months, with two of these four becoming long-term survivors. One patient lived for over thirteen years and another for over twenty-four years.