We consider the beam orientation optimization (BOO) problem for total marrow irradiation (TMI) treatment planning using intensity modulated radiation therapy (IMRT). Currently, IMRT is not widely used in TMI treatment delivery; furthermore, the effect of using non-coplanar beam orientations is not known. We propose and implement several variations of a single neighborhood search algorithm that solves the BOO problem effectively when gantry angles and couch translations are considered. Our work shows that the BOO problem for TMI cases can be solved in a clinically acceptable amount of time and leads to treatment plans that are more effective than the conventional approach to TMI. © 2010 Elsevier B.V. All rights reserved.