Objective: There is a persistent theory that birth stress and subsequent brain pathology play an important role in the manifestation of left-handedness. Evidence for this theory, however, is mixed and studies are often beset with problems related to small sample sizes and unreliable health reports. Method: To avoid these issues, this study used a sample of approximately 10,000 children from the British Cohort Study. The study contains objective birth-health reports and comprehensive measures of socioeconomic status, handedness, cognitive ability, and behavioral/health issues. Results: Regression analyses showed that variables associated with birth stress affected cognitive/behavioral/health outcomes of the child. Despite this, these same factors did not affect the direction or degree of hand preference. Conclusions: We have therefore demonstrated a dissociation whereby adverse birth factors affect the brain s cognitive ability, but not handedness, and by implication, cerebral lateralization. The study also demonstrated a link between left-handedness and reduced levels of cognitive ability. This link cannot be due a generalized birth-stress mechanism and may be caused by specific mechanisms related to changes in cerebral dominance.