Description: Organs from hypernatremia (elevated Na + ) donors when used for transplantation have had dismal outcomes. However, islet isolation from hypernatremic donors for both transplantation and research applications has not yet been investigated. A retrospective analysis of in vivo and in vitro islet function studies was performed on islets isolated from hypernatremic (serum sodium levels ≥ 160 meq/l) and normal control (serum sodium levels ≤ 155 meq/l) donors. Twelve isolations from 32 hypernatremic and 53 isolations from 222 normal donors were randomly transplanted into diabetic NOD Scid mice. Sodium levels upon pancreas procurement were significantly elevated in the hypernatremia group (163.5 ± 0.6 meq/l) compared with the normal control group (145.9 ± 0.4 meq/l) ( P 〈 0.001). The postculture islet recovery rate was significantly lower in the hypernatremia (59.1 ± 3.8%) group compared with the normal (73.6 ± 1.8%) group ( P = 0.005). The duration of hypernatremia was inversely correlated with the recovery rate ( r 2 = 0.370, P 〈 0.001). Furthermore, the percentage of successful graft function when transplanted into diabetic NOD Scid mice was significantly lower in the hypernatremia (42%) group compared with the normal control (85%) group ( P 〈 0.001). The ability to predict islet graft function posttransplantation using donor sodium levels and duration of hypernatremia was significant (ROC analysis, P = 0.022 and 0.042, respectively). In conclusion, duration of donor hypernatremia is associated with reduced islet recovery postculture. The efficacy of islets from hypernatremia donors diminished when transplanted into diabetic recipients.