Under the mentorship of at first Michael E. DeBakey at BCM, and then Denton Cooley at the THI, he performed research on the testing of LVADs as a form of MCS.

He continued to lead and become significantly influential in heart surgery and the development and clinical implementation of LVADs and his surgical career at the THI has spanned over fifty years.

Other positions have included chief of the transplant service at Baylor St. Luke's Medical Center (part of the Catholic Health Initiatives system) in Houston.

Both his parents were teachers[1][2] and his grandfather nicknamed him "Bud" after a distant cousin who was killed in a West Texas saloon shootout at the turn of the nineteenth century.

[5] As a medical student at BCM in 1964, he assisted in experimental total artificial hearts (TAH) research, which placed him under the mentorship of Michael E. DeBakey, Domingo Liotta and Denton A. Cooley,[1][6] who five years later, controversially became the first to implant one.

[7] In 1966, at the age of 25, while still a medical student of DeBakey, who he described as a “tough taskmaster”,[8] an experience with a teenager who had just had an aortic valve repair, left a lasting impression on him.

[1] Upon graduating with an MD in 1967, he also received the DeBakey Award for Outstanding Surgical Student[11] before then completing his residency at Baylor Affiliated Hospitals in 1968.

[12] In 1985, during his tenure on the advisory board of the National Heart, Lung, and Blood Institute (NHLBI), Frazier recommended that research be initiated on a TAH that would be fully implantable and that would allow people to be discharged and to live a normal lifestyle.

This encouraged a living lining of endothelial cells resembling the inner surfaces of arteries and veins and hence required less blood thinning drugs.

[6][12] In March 2011, Craig Lewis was suffering from amyloidosis and not eligible for heart transplant due to the severity and extent of the disease, affecting also his kidney and liver.

Their TEDMED talk introduced them to Daniel Timms, who was driven to find a technological resolution and whose father had died of heart failure.

[27] Published in 2018, a book entitled Ticker, recounts the story of Frazier's task to construct a sustainable totally implantable artificial heart.

[28] The author describes Frazier sharing traits with pioneers in other fields[29] and how for over half a century been driven by the desire to save lives.

[29] In 2018, ProPublica and the Houston Chronicle published an investigation into Frazier, claiming that he had been "accused of violating federal research rules and skirting ethical guidelines, putting his quest to make medical history ahead of the needs of some patients.