Introduction: Low serum albumin in the chronic kidney disease population is a strong predictor of morbidity and mortality. Preoperative hypoalbuminemia has also been shown to be a risk factor for post operative complications in patients undergoing various surgical procedures. Children with chronic kidney disease often have low serum albumin, either as a result of inflammation, malnutrition or from urinary protein losses. Delaying transplantation until hypoalbuminemia is corrected may be the optimal strategy but this may not allow pre-emptive transplantation, the preferred strategy. There are no data in the pediatric renal transplant literature assessing how commonly children are transplanted with very low serum albumin (< 2.5 g/dL) and what its impact on post-transplant outcomes. The aim of our study was to answer these two questions. Methods: Records of all children receiving their first (standard criteria) kidney-only transplant in the US from January 2000-September 2010 were obtained from the Organ Procurement and Transplantation Network (OPTN). Data collected included recipient and donor demographics, pre-operative serum albumin (at time of registration), and variables related to the transplant itself. The primary outcome measure was graft loss. Cox regression analyses were performed to determine the independent effect of serum albumin on time to graft loss, controlling for patient, donor and transplant characteristics. Results: Of the 5,922 transplants, 302 (5.1%) had a very low serum albumin level at registration. Rates of transplantation with very low serum albumin varied significantly across the 11 OPTN geographic regions (Chi-square on 10 degrees of freedom=44.8, p< 0.01), with the lowest region transplanting 12 of 566 (2.1%) children in the very low serum albumin category and the highest transplanting 46 of 562 (8.2%). Serum albumin levels were inversely associated with graft failure. In the Cox proportional hazards model of time to initial graft failure (1067 events of 5,816 transplants under observation with an average follow-up time of approximately 3.3 years), each 1 g/dL increase in serum albumin was associated with a 20% reduction in risk of graft failure (adjusted hazard ratio =0.79, 95% CI: 0.73-0.86). Using categorical analyses of serum albumin in an otherwise similar model, both very low serum albumin level (< 2.5 g/dL) and low serum albumin (2.50 to 3.49 g/dL) were associated with higher adjusted hazards of graft failure of 1.58 (95% CI: 1.25-2.01) and 1.24 (95% CI: 1.08-1.43), respectively relative to the reference category of 3.50+ g/dL. Conclusions: Considerable regional variation exists amongst transplant centers in the US with respect to transplanting children with significant hypoalbuminemia. A very low serum albumin level is an independent risk factor for graft failure. Whether graft failure is a consequence of the low serum albumin or a reflection of a higher inflammatory milieu in such patients, needs to be explored. Transplant centers as well as patients need to be aware of this risk and make informed decisions regarding the optimal timing of transplantation, weighing the risks and benefits of prolonging wait times in patients with hypoalbuminemia while measures are instituted to help improve their overall health status.