Valsartan/Sacubitril (V/S) has recently been approved by the FDA for pediatric (>1yo) heart failure. While the PANORAMA-HF trial is ongoing, encouraging 12-week results prompted early FDA-approval. Over the last 4 years, our center has been prescribing V/S off-label for those pediatric heart failure patients who did not respond to ACEi/ARB or were at high risk for deterioration. This is the first report of clinical use of V/S for children, describing safety, tolerability and efficacy in pediatric heart failure patients. Retrospective single center study of 36 patients ≤18 yo (including 8 infants <1 yo) who received V/S off-label between 2015-2019. Underlying diagnosis was CHD in 12 (7 single ventricle), DCM in 24 (13 idiopathic, 4 Duchenne, 4 post-chemotherapy, 3 post heart transplant). Most (n=33) received ACEi/ARB prior to starting V/S. Ten patients were initiated on V/S while weaning milrinone, whereas 26 were in compensated heart failure, receiving betablockade (n=26) and spironolactone (n=14). Median age at initiation of therapy was 4.3y (R 26d-18y). Mean duration of therapy was 426 (±369) days; 22 patients reached at least 75% of pediatric target dose (3.1mg/kg bid). Inability to reach target doses was due to clinical deterioration (3 received heart transplant, 2 deaths), renal compromise (4), hypotension (2) or insufficient time on drug (3). V/S had to be discontinued for hypotension in 1 patient (infant) and temporarily held for renal side effects in 2 patients (also infants). Mean potassium, BUN or creatinine did not increase over duration of study. Mean LVSF improved during therapy from 17.1 ± 8.7 to 21.4 ± 10.4% (p=0.004) and LVEF improved from 28.9 ± 11.9 to 39.8 ± 14.8% (p=0.0002). Mean LVEDD Z-scores decreased from 5.5 ± 3.7 to 4.3 ± 3.0 (NS; p=0.06). Ross scores improved in 12 pts, remained stable in 13, and worsened in 11. Six Ross I pts remained stable; of 7 Ross II pts, 1 improved to Ross I, whereas 6 remained stable; of 11 Ross III pts, 2 improved to Ross I, 4 to Ross II, 1 remained stable, 3 were listed for HTx, and 1 with Duchenne died; of 12 Ross IV pts, 2 improved to Ross I, 3 improved to Ross II, 6 were listed for HTx, and I died from leukemia. V/S appears safe and well tolerated in most pediatric patients including infants. Our study cohort was small and included high risk heart failure patients, of which 1/3 clinically improved after starting V/S.