Calderwood was an expert panel member on the Morecambe Bay Investigation, commissioned by the Department of Health to look into the maternity and neonatal services at Morecambe Bay NHS Foundation Trust between January 2004 and June 2013. In March 2013, as the Scottish Government's senior medical officer for women's and children's health, she helped launch Maternity Care Quality Improvement Collaborative. Calderwood was NHS England's national clinical director for maternity and women's health 2014-2015. and in this role promoted the first friends and family test in 2014.
Calderwood was Acting Deputy Chief Medical Officer in Scotland, supporting Dr Aileen Keil who had been Acting Chief Medical Officer of Scotland from April 2014 following the retirement of Sir Harry Burns from the post in April 2014. In February 2015, Calderwood was announced as the new Chief Medical Officer of Scotland, succeeding Burns.
Resignation
In April 2020, during the COVID-19 pandemic in Scotland, Calderwood apologised for visiting her second home in Earlsferry, Fife, about 44 miles from her home in Edinburgh, on consecutive weekends with her family, contravening the advice issued by herself in her high-profile role as Chief Medical Officer for Scotland, her own office, and the Scottish Government to stay at home and help limit the spread of the virus. On 5 April 2020 she was visited at home by officers from Police Scotland and warned about her conduct. In a government press conference later that day, she admitted she had visited her holiday home more than once during lockdown and apologised. The most recent visit had been on 4 April 2020. Scottish Labour's shadow health secretary, Monica Lennon, called for Calderwood's resignation, saying "The CMO has undermined Scotland’s pandemic response and if she doesn't offer her resignation the First Minister should sack her." On the afternoon of the 5 April 2020 First Minister Nicola Sturgeon announced that Dr Calderwood would be "withdrawing from media briefings for the foreseeable future" and explained that the government would be revising its public information campaign. Several hours later, on the evening of 5 April 2020, Calderwood resigned. She issued this statement: "People across Scotland know what they need to do to reduce the spread of this virus and that means they must have complete trust in those who give them advice". The following morning, Sturgeon told BBC Breakfast that she and Calderwood had had a "long conversation" on the evening of the 5 April. Sturgeon reported that as a result of this conversation she and Calderwood mutually agreed that Calderwood should stand down from being Chief Medical Officer for Scotland.