This study aimed to evaluate the survival of a cohort of liveborn infants diagnosed with encephalocele during a 20-year period and the variation of such survival by selected demographic and clinical characteristics. We reviewed data from the Metropolitan Atlanta Congenital Defects Program (MACDP) to ascertain all live births diagnosed with encephalocele (n = 83) from 1979 to 1998. Of these, 66 (79%) had isolated defects. Among 70 liveborn infants with site of the defect specified, 50 were classified as having posterior and 20 with anterior defects. To identify their vital status, we used data from MACDP hospital records and vital records from the State of Georgia supplemented by linking registry data with the National Death Index from 1979 to 1999. Among children with encephalocele, 76.0% of the deaths (19/25) occurred during the first day of life. The survival probability to 1 year of age was 70.8%[95% confidence intervals (CI) 60.9, 80.7] and to 20 years of age was 67.3%[95% CI 55.7, 78.8]. In multivariable analysis, factors associated with increased mortality were low birthweight (<2500 g) [relative risk (RR) 5.18; 95% CI 2.13, 12.63], presence of multiple defects (RR 2.82; 95% CI 1.19, 6.69) and black race (RR 2.36; 95% CI 0.95, 5.85). Overall survival for infants with multiple defects (41.2%) was significantly poorer than survival among those with isolated defects (74.3%). A 70% decrease in risk of mortality was observed among infants born with encephalocele during 1989-98 compared with those born during 1979-88, but this decrease was evident only among cases with low birthweight (RR 0.29; 95% CI 0.01, 0.90). This study highlights the prognostic importance of multiple defects and low birthweight for infants with encephalocele and identifies a statistically significant difference in survival by race. This information is useful for clinicians and families who must plan for the long-term care of affected children.