Background There is international interest in the active involvement of patients and the public. However, consensus on how best to optimize its application is currently unavailable. Objective To identify and assess the underlying principles of patient and public involvement (PPI) in health and social care services, research, education and regulation across medicine, dentistry and nursing. Design A four‐phase methodology: (i) an extensive systematic review of published and grey literature; (ii) inductive thematic analysis of review findings; (iii) development of best practice principles; and (iv) consensus testing of identified principles using a modified Delphi methodology. Setting and participants Twelve systematic reviews and 88 grey literature publications were reviewed leading to the unique identification of 13 principles later assessed by 18 PPI experts. Results Essential consensus (>75% agreement) was obtained for nine principles reviewed. Working in equal partnership and sharing information achieved the highest consensus rates: 16/17 essential 94.1%; 1/17 desirable 5.8%. The four remaining principles that failed to reach essential consensus were categorized as desirable by expert respondents. No principles were considered irrelevant. No alternatives were suggested. Discussion Expert respondents suggest essential principles must be achieved to optimize PPI best practice. To advance PPI practice, desirable principles should also be aspired to wherever possible. Conclusions This study's innovative approach advances existing knowledge by providing previously unavailable consensus about PPI best practice. Research findings hold important theoretical and practical implications for educators, regulators, researchers and practitioners looking to effectively work together.