Hodgkin used X-ray crystallography to aid in the determination of the structural arrangement of the atoms in simple salts and minerals, such as thallium alkyl halides. She discovered that the atoms in crystals are arranged in regular repeating patterns.
In 1933 she went to work on her doctorate degree at Cambridge with John Desmond Bernal. Bernal had previously worked for five years with William H. Bragg (an early pioneer of crystallography) at the Royal Institution. Hodgkin and Bernal recorded the first X-ray diffraction patterns of globular proteins, an immensely difficult task due to the lack of technology and the size and complexity of the proteins being studied.
She then returned to Oxford University and began research on sterols including cholesterol iodide and over 100 steroids. She determined in detail the exact 3-D structure including positions of atoms and the stereochemistry at each carbon. This work was a breakthrough in crystallography since it was the first analysis based on three dimensional calculations.
She continued to work at Oxford and Cambridge Universities and became a Fellow and chemistry tutor at Somerville College, Oxford. One of her pupils at this time was Margaret Thatcher who worked in Dr. Hodgkin's laboratory for her fourth year research project.