Dr O’Keefe graduated from the University of Melbourne in 1980 and subsequently worked at the Austin Hospital before commencing dermatology training in 1983. After attaining his Fellowship from the Australasian College of Dermatologists he worked in Glasgow from 1986 – 1987, where he met his wife, Irene. On returning to Melbourne, he worked as a sessional dermatologist at St Vincent’s Hospital and the Peter MacCallum Cancer Institute and commenced a private dermatology practice. 

He maintained a part-time practice in dermatology during his pathology training, working half-time in his dermatology practice in association with A/Prof Chris Baker. The other half was spent working in dermatopathology, initially at Dorevitch Pathology and from 2001 in his own dermatopathology laboratory, Dermpath, until 2011 when he joined Melbourne Pathology. 

From 2015 Dr O’Keefe increased his time in clinical dermatology until his retirement in 2018, while continuing consultancy in dermatopathology with Melbourne Pathology. In recent years he has been involved in establishing a Diploma in Dermatopathology for the College of Pathologists.