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Julia Chain, Garretts managing partner and an Andersen Worldwide partner, is to leave the firm this year as soon as she has a concrete job offer.
Chain said she would not be continuing in private practice and had decided to "make a change of direction that allows me to develop further my managerial experience".
She denied that the attempted merger with Wilde Sapte, which failed last month, had anything to do with her decision.
"I'd practically made the decision before that," she said.
Her role has shrunk recently from when she first took over as managing partner from Colin Garrett in the summer of 1993.
At the end of last year Andersens tax partner Peter Ridley was appointed to a newly-created role of "managing director" of Garretts to ensure the law firm worked together with its accountancy parent.
Earlier Chain had been elbowed aside from a national role and put in charge solely of the London office when Dundas & Wilson joined the Andersen network.
Of this change, Chain said: "Everyone seems to think it was a demotion. It was a most wonderful thing. It was far too much for one person to have to play about with eight separate locations."
But she conceded: "The job has changed considerably. We've been very successful at building the practice. But when you get all the systems in place and up and running there is much less to do. My work has become more client orientated - as any managing partner job would be."
The firm was now consolidating and "growing at a much less hectic pace than we were, thank God," she said.
"I've done the job I wanted to do and I've changed course while doing it."
She would not comment on who would replace her as managing partner or if the role would continue to exist.
Nick Prentice, managing partner of Andersen tax and legal in Europe, said: "We have discussed a number of options with Julia, but we respect her decision to change direction. When she leaves later this year, she will take with her the gratitude of both Garretts and Arthur Andersen."