ABSTRACTBACKGROUND AND PURPOSEMidline shift determined on magnetic resonance imaging (MRI) or computed tomography (CT) images is a well‐validated marker of mass effect after large hemispheric infarction and associated with mortality. In this study, we targeted a population with moderately sized strokes. We compared midline shift to other imaging markers and determined their ability to predict long‐term outcome.METHODSMRI scans were studied from the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) cohort. Midline shift, acute stroke lesion volume, lesional swelling volume, change in ipsilateral hemisphere volume, the ratio of ipsilateral to contralateral hemisphere volume, and the reduction in lateral ventricle volume were measured. The relationships of these markers with poor outcome (modified Rankin scale score 3–6 at day 90) were assessed. Receiver‐operating characteristic (ROC) curves were generated to compare the performance of each metric.RESULTSOf the 71 included patients, 59.2% had a poor outcome that was associated with significantly larger values for midline shift, lesional swelling volume, and ratio of hemisphere volumes. Lesional swelling volume, change in hemisphere volume, ratio of hemisphere volumes, and lateral ventricle displacement were each correlated with midline shift (Spearman r = .60, .49, .61, and −.56, respectively; all P < .0001). ROC curve analysis showed that lesional swelling volume (area under the curve [AUC] = .791) predicted poor outcome better than midline shift (AUC = .682). For predicting mortality, ROC curve analysis showed that these three markers were equivalent.CONCLUSIONThe ratio of ipsilateral to contralateral hemisphere volume, baseline lesion volume and lesional swelling volume best predicted poor outcome across a spectrum of stroke sizes.