It is said of Dr. Wangensteen that he had twenty original ideas a day. As an inventor, his greatest achievement was the development in 1932 of the Wangensteen gastric suction system used to aspirate gas and fluid from the stomach and intestines. When the stomach suffers some sort of trauma, such as from a wound or an operation, a blockage may form in the intestines. Back in the 1930s nobody knew what this blockage was, but they were sure of one thing – it killed people. Wangensteen found that he could relieve these obstructions simply by threading a little tube through a patient’s nose, down the esophagus and into the stomach and intestines, and vacuuming them out. This technique spread throughout the medical world, saving literally hundreds of thousands of lives. Twelve years later it was reported that no greater practical advance in medicine had been made on this continent. It was never patented, but was dedicated to the public for the benefit of all. It was the belief of Dr. Wangensteen that his concepts and inventions should be available for everyone to use.

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The Wangensteen suction tube has proven useful in abdominal surgery to prevent the accumulation of gas and fluid in the stomach and intestine after a surgical operation, avoiding the nausea and vomiting that the patient might otherwise suffer. Every hospital in American uses the technique and, as one University faculty member put it, "the Wangensteen tube is a household word in surgical clinics." Throughout most of his professional career, he continued to modify and improve methods and devices for intestinal decompression.

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In 1962, Wangensteen developed a techniques to treat ulcers by deep freezing the patient’s stomach. A balloon attached to a tube is lowered into the stomach and inflated with a coolant to refrigerate the ulcer. The technique apparently works to reduce the pain of gastric disorders by destroying tiny nerve endings that cause pain and by impairing the stomach’s ability to make acids and other secretions.

He also designed many original surgical instruments, and was instrumental in the early development of open-heart surgery.  Wangensteen's "strong and abiding interest in research" is the reason that open-heart surgery was born at the University of Minnesota, says Dr. John S. Najarian, Wangensteen's successor as chairman of the Department of Surgery.

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He was one of the greatest teachers of surgery in the United States. Two of his former students, Dr. Christiaan Barnard and Dr. Norman Shumway, performed the first heart transplant surgeries.  Barnard is the South African surgeon who performed the first human heart transplant in 1967, and Shumway is the American surgeon who devised the technique for heart transplants. Shortly after  Barnard’s revolutionary heart transplant operations in the late 1960s, an article in Business Week magazine about the University of Minnesota Medical School traced that surgery back to Wangensteen's laboratories and teaching methods.

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Other world famous surgeons who trained under Wangensteen credit him for giving them the encouragement and freedom they needed to explore new ideas, new methods, and new devices, including: Dr. F. John Lewis, who led the world's first successful open-heart surgery in 1952 using hypothermia; Dr. C. Walton Lillehei, who introduced the technique of cross-circulation in 1954; and Dr. Richard A. DeWall, who introduced the heart-lung machine a year later. Heart surgeries using a refined version of that heart-lung machine are still performed hundreds of times a day all over the world.

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Wangensteen founded the Surgical Forum at the American College of Surgeons to provide up-and-coming surgeons an opportunity to share their ideas and research findings. In 1982, the year after he died, the Department of Surgery established the Wangensteen Award for Excellence in Teaching in his honor.

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He has left a legacy unparalleled in the field of American surgery. His dedication as a clinical surgeon, his prowess as a medical educator, and his enthusiastic originality in scientific investigation ensure him a permanent place among the very great surgeons of the world.