In 1991, O'Connor became a professor of orthopedics at the Mayo Clinic in Florida, becoming chair of the department of orthopedic surgery in 2005. There, she operated on bone and soft tissue tumors, and also performed knee and hip replacements. Her focus areas were knee osteoarthritis, knee replacement surgery, limb salvage surgery, and health care process improvement. She also researched the differences between how women and men feel knee arthritis and the impact of stem cell injections on knee arthritis. Her research has been published in Clinical Orthopaedics and Related Research, the Journal of Arthroplasty, and The Journal of Bone and Joint Surgery.
