His major work Tzitz Eliezer is an encyclopedic treatise on halachic questions, viewed as one of the great achievements of halachic scholarship of the 20th century. Though he wrote numerous books and articles in all fields of halacha, he was best known for his decisions on medical dilemmas. He addresses in his volumes complex medical questions including fertility, abortion, organ transplantation, euthanasia, sex reassignment surgery, autopsies, smoking, cosmetic surgery, and medical experimentation.