Early markers of atopic predisposition are needed for targeting allergy preventive measures to high-risk infants. An elevated cord serum immunoglobulin E (CS-IgE) level is considered a risk factor for subsequent allergy in childhood. However, the previous studies have not assessed the predictive value of CS-IgE in a follow-up extended to adulthood. We aimed at clarifying whether CS-IgE is useful in predicting subsequent atopic manifestations up to age 20 yr. A cohort of 200 unselected, full-term newborns were prospectively followed up from birth to age 20 yr. The CS-IgE level was successfully measured in 190 subjects at birth. The subjects were re-examined at ages of 5, 11 and 20 yr with assessment of the occurrence of allergic symptoms during the preceding year, skin prick testing and measurement of serum total IgE. An elevated CS-IgE level was associated with allergic symptoms and skin prick test positivity at age 5 yr (p = 0.03 and 0.01), with allergic rhinoconjunctivitis at age 20 yr (p = 0.04) and with an elevated serum total IgE at ages of 11 and 20 yr (p = 0.02 and 0.01). The sensitivity of CS-IgE, i.e. the probability of an elevated CS-IgE in an infant who subsequently develops atopy, in predicting skin prick test-verified atopy at ages of 5 and 20 yr was 50% and 26%, respectively. The combination of elevated CS-IgE and positive family history of allergy was strongly associated with subsequent atopic manifestations. Nevertheless, it showed a reduced sensitivity as compared to CS-IgE or family history of allergy. We conclude that an elevated CS-IgE level predicts subsequent atopy up to age 20 yr.