She is ending her tenure at the Dunedin theatre after five ''rewarding'' years. Ms Macgregor (46) announced she will be leaving next month.
The decision was ''difficult but necessary'', she said.
''Running a theatre company, you give over a huge part of yourself and your life. So now is the time for me to re group, re balance, and re invest in my future as an artist and practitioner.''
The vacant position provided an ''exciting opportunity for a new visionary to take the reins'' and lead the theatre to its next phase, she said.
Ms Macgregor plans to remain in Dunedin and work as an independent director, actor and photographer.
Theatre board of trustees chairman Ray Tobin said the Fortune was ''very sad'' to lose Ms Macgregor.
''[We] have been very fortunate to have had someone of Lara's calibre and talent.
''It has been an extreme pleasure working with Lara and I hope we will see her talents in the theatre again in the future, directing and acting,'' Mr Tobin said.
A replacement for Ms Macgregor was expected to be announced later this year, he said.