Shona Robison conceded her role as health secretary in the Scottish Government had been “at times very challenging” as she quit Nicola Sturgeon’s cabinet.
She had taken on the role in 2016 when Ms Sturgeon, her close friend, became the First Minister.
A failure to meet key NHS waiting times resulted in opposition politicians in the Scottish Parliament heaping pressure on her.
She had also faced calls to quit after financial problems in NHS Tayside – which includes her Dundee East constituency.
Health board chiefs there used £3.6 million from its endowment fund, which is made up of donations from the public or bequests in wills, to help it break even in 2013-14.
In her resignation letter Ms Robison, a former public health minister, said she had reached a point in life where she “would be best to step down from a role in government”.
Ms Robison, who split from her husband, former SNP depute leader Stewart Hosie in 2016, stated: “This last year has been particularly challenging for me personally, losing both my parents, having a health scare of my own and some big changes in my personal life.”
She thanked Ms Sturgeon for her “support during these difficult times”, and added: “I have entered a new chapter of my life, including a new relationship, where it would be good to take time to focus on those closest to me, who have too often had to come second place to my job, which has been hard for us all.”
The First Minister said while Ms Robison was no longer part of the cabinet, she would continue to seek her counsel “as a colleague and a friend”.
Ms Sturgeon thanked her for her “hard work in government” and added: “Our friendship has always been extremely important to me.”
Ms Robison is succeeded as health secretary by Jeane Freeman – a former student member of the Communist Party who went on to become an adviser to former Labour first minister Jack McConnell.