To provide adequate care to children with acute malnutrition, different management protocols have been in use, including the WHO standard guideline and a simplified protocol. The latter, used in Venezuela since 2020, has adopted three simplifications: 1) Expanded criteria for treatment admission; 2) Use of a single treatment product; 3) Simplified dosage: use of 2 sachets per day to treat SAM cases and 1 sachet per day to address MAM cases, regardless of weight. Our study compares the effectiveness, length of stay and programmatic costs of the simplified protocol and the WHO standard guideline in addressing acute malnutrition in children aged 6-59 months in Venezuela from February to August 2024. A total 229 children were enrolled in a prospective cohort study. Monitoring was continuous up to 16 weeks of treatment, evaluating key indicators including weight gain, recovery time, survival, recovery and default rates, number of sachets of RUTF consumed and implementation costs. Baseline characteristics were similar between cohorts, with most cases being moderate in both the standard (90.9%) and simplified (86.6%) cohorts. Both protocols demonstrated similar anthropometric improvements and recovery trajectories throughout follow-up, with no significant differences (p > 0.05). However, the simplified protocol showed higher recovery rates overall for MAM and SAM (70.1% vs 59.4%, p=0.031), although default rates remained high in both protocols (24.8% in the standard protocol vs. 18.7% in the simplified protocol). The simplified protocol presented reduced costs by 15% ($133 vs $157 per recovered child). These results suggest that the simplified protocol, using a single product and an adapted dosage, is as effective as the standard protocol for treating children with acute malnutrition in Venezuela. The findings support wider implementation of the simplified protocol particularly in resource-limited settings. Further research is needed to optimize protocols and improve adherence to reduce default rates. The study protocol was registered on ClinicalTrials.gov (NCT06287827) as an observational study.