Dr Peter Carter, the RCN's chief executive and general secretary, will step down from the role as soon as a successor is found.
Dr Carter has been in the post for the past eight years, and has presided over issues such as the NHS reorganisation in 2012, and the recent pay dispute over the government's refusal to award nurses a consolidated one per cent pay rise.
Dr Carter said: 'I have thoroughly enjoyed my time at the RCN. It is just over eight years since I joined the college and it has been a wonderful time in my career. The challenges when I joined the RCN were significant and with the support of the RCN council and my colleagues we have taken forward the work of the RCN on behalf of our members.
'This has involved change in the way that the College works and has resulted in financial stability and a huge increase in the membership of the College. The RCN credibility with stakeholders is very high and the college brings huge added value to the health agenda throughout the United Kingdom and internationally' he added.
Before he accepted the post of chief executive of the RCN, he spent 12 years as the chief executive of the Central and North West London Mental Health NHS Trust. He received an OBE in 2006 for his services to the NHS. He began his career as a psychiatric nurse in St Albans before moving on to a role in the adolescent unit at the Hill End Hospital, also in St Albans.
Michael Brown, the RCN's chair of council said: 'It is with great regret that today I have accepted Dr Peter Carter's resignation as chief executive of the RCN. In the eight years Peter has been with the RCN, the College has moved forward significantly and has improved under his management in difficult times within healthcare.'
A replacement has not yet been announced but Dr Carter will remain in the role until a successor is found.
Mr Brown added: 'Peter has been a champion, not only for our members but the whole nursing family and health services during his time with the College. He has really raised the profile of both nursing and the RCN and has consistently championed the very best in patient care. We thank him for all he has done for members and the College over the years.'