Unanticipated reorientation of otherwise stationary nanocrystals during MicroED experiments could introduce errors into data reduction routines adapted from X-ray crystallography, as these generally assume a crystal is rotating unidirectionally about a single known axis. To determine whether lattice reorientations have a significant impact on conventional MicroED datasets, we interrogated data recorded from continuously rotating crystals diffracted by a low-flux electron beam. We then searched for evidence of unmodeled reorientation of continuously rotating crystals during data reduction. Data reduced from biotin and Zn(II)-methionine at 100 K and Co(II)-porphyrin at 293 K, in this case using XDS (5), revealed evidence that changes in crystal orientation were occurring independent from the rotation of the sample stage (Fig. ). After achieving initial indexing solutions, data were reprocessed holding certain geometric parameters often refined by XDSunit cell constants, rotation axis, and orientation -fixed. We tracked the estimated crystal mosaicity determined by XDS for each frame of data. We expected that anomalous intensity fluctuations in diffraction tilt series might be interpreted by data reduction software as increased mosaicity, despite authentically being due to beam-induced reorientations. Supporting this hypothesis, the estimated mosaicity of Zn(II)-methionine and biotin crystals increased with accumulated fluence, as a crystal rotated. This was not true for Co(II)-porphyrin crystals diffracted under equivalent conditions, suggesting this might be a symptom of reorientation. We then reprocessed the same tilt series datasets while allowing XDS to refine only crystal orientation in small batches of images. Performing these refinements over 2.5 degree wedges at a time somewhat abated the trend of inflated mosaicity, especially for data from Zn(II)-methionine crystals (Fig 5A ). Most of these Zn(II)-methionine datasets also granted decreased R-factors when processed allowing for orientation refinements; in one case a decrease of as much as 7% in R merge and 9% in R meas was observed (Supplementary Table ). Following delivery of ~1.75 e - /Å 2 , we noted a generally improved agreement between reflection positions predicted by XDS and those seen in the experimental frame when orientation refinements were implemented for the Zn(II)-methionine tilt series datasets (Fig 5B ). While allowing crystal orientation to be refined over small wedges of data can reduce errors due to reorientation, MicroED data reduction may be limited by the minimum size of a wedge of angular data that can be refined.