© 2015 Elsevier B.V. Background We recently reported that left versus right hemisphere cerebral infarctions patients more frequently have worse outcomes. However our clinical experience led us to suspect that the incidence of malignant middle cerebral artery infarctions (MMCA) was higher in the right compared to the left hemispheric strokes. Objective To determine whether laterality in MMCA stroke is an important determinant of stroke sequelae. Methods A systematic search was performed for publications in PubMed using "malignant middle cerebral artery and infarction". A total of 73 relevant studies were abstracted. Results MMCA laterality data were available for 2673 patients, with 1687 (63%) right hemispheric involvement, thus right being more commonly associated with MMCA (binomial test, p < 0.05). While mortality rates were similar, right hemispheric MMCA (n = 271) had mortality of 31% (n = 85) whereas left hemispheric MMCA (n = 144) had mortality of 36% (n = 53), morbidity rates were worse on the right. Conclusion MMCA stroke appears to be more common on the right, and this laterality is also associated with significantly higher morbidity. Further prospective studies are needed to more completely understand the nature of this laterality as well as test possible new treatments to reduce mortality and morbidity associated with MMCA.