If an ESOP aquires more than 50% of the company, is that a change in control for purposes of 280G?

There is no exception in the 280G Regulations for ESOP transactions. The key issue is whether an ESOP is condsidered to be a group of people acting together in acquiring majority control. 1.280G-1 Q-27. In some cases, the ESOP is considered to be a collection of minority interests, in others it is considered a controlling entity. Relevant facts would be who controls the vote. If there is a lot at stake, get a tax opinion or private letter ruling.