The aim of this study was to estimate the cost-effectiveness of a very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids compared with a conventional low-protein diet (LPD) in Vietnam. The study was conducted from payer (base case), patient, and societal perspectives. A Markov model simulated costs and quality-adjusted life-years (QALYs) for patients with chronic kidney disease stage 4 or 5 (CKD4+) who were followed up during their lifetimes. Patients received a VLPD (0.3- to 0.4-g/kg/d diet) supplemented with ketoanalogues (5 kg/d [1tablet]) versus LPD (0.6 g/kg/d, mixed proteins). In each model cycle, patient transitions among the health states-CKD4+ (nondialysis), dialysis, and death-were based on transition probabilities taken from the published literature. The time horizon covered the cohort's lifetime. Utilities and costs were estimated from literature review and projected for the lifespan considered in the model. Probabilistic and deterministic sensitivity analyses were performed. The ketoanalogue-supplemented VLPD increased survival and QALYs compared with the LPD. From a payer's perspective, total cost of care in Vietnam was ₫216,854,268 (€8684/$9242) per patient with LPD versus ₫200,928,819 (€8046/$8563) per patient with a supplemented VLPD (sVLPD) (difference, -₫15,925,449 [-€638/-$679]). From a patient's perspective, total cost of care in Vietnam was ₫217,872,043 (€8724/$9285) per patient with LPD versus ₫116,015,672 (€4646/$4944) per patient with sVLPD (difference, -₫101,856,371 [-€4,079/ -$4341]). From a societal perspective, total cost of care in Vietnam was ₫434,726,312 (€17,408/-$18,527) per patient with LPD versus ₫316,944,491 (€12,692/ $13,508) per patient with sVLPD (difference, -₫117,781,820 [-€4716 €/$5020). Ketoanalogue-supplemented VLPD lowered costs compared with LPD in all 3 perspectives considered.