Any form of EB, especially those with generalized cutaneous disease activity, may result in death during infancy or early childhood. In addition, it is known that many patients with the Hallopeau-Siemens variant of recessive dystrophic EB (RDEB-HS) develop life-threatening squamous cell carcinomas (SCCs) beginning as early as the second decade of life. Data are lacking, however, as to the risk of premature death over time, either by major EB type or subtype. To address this, we have performed lifetable analysis, utilizing data on 1738 EB cases available through 11/1/94 (EB simplex, Dowling-Meara [EBS-DM], 71; EBS, other [EBS-O], 1005; Herlitz junctional EB [JEB-H], 26; non-Herlitz JEB [JEB-O], 133; dominant dystrophic EB [DDEB], 251; RDEB-HS, 115; RDEB, other [RDEB-O], 137) within the National EB Registry on whom up to 8 yrs of longitudinal data existed on the occurrence and date of death. When only the major EB types (EBS, JEB, DDEB, RDEB) were considered, risk of mortality from all causes ≥ 0.70% by age 50 was observed with only JEB and RDEB. By 1 yr of life, the probability of death was 28.57% in JEB, increasing to 36.30% and 43.31% by ages 5 and 65. Whereas no mortality was noted in RDEB before age 2, the cumulative risk of death in RDEB was 0.45%, 1.04%, 3.01%, 8.35%, 24.96%, and 44.18% by ages 5, 10, 15, 20, 30, and 40, respectively. By age 30 the risk of mortality from all causes for RDEB-O and RDEB-HS was 7.85% and 40.17%. When stratified by major EB type, 22.8% and 3.8% of all EB deaths resulted from infection or failure to thrive. When stratified by major EB subtypes, infectious deaths were most prevalent in JEB-O (34.0%) and JEB-H (22.2%). In contrast, 54.8% of all RDEB-HS deaths resulted from SCC, and only 12.9% from infection. These findings demonstrate that JEB patients are at great risk of death early in childhood, whereas increased risk of mortality in RDEB-HS is primarily a problem on or after age 20, closely following the known timing of SCCs in the latter patients.