ABSTRACT Objective To analyze the cost-effectiveness of weekly somatrogon compared to daily growth hormones (GH-d) in the pediatric population of Spain with growth hormone deficiency (GHD). Methods Markov model with two states (patients with or without GH-d or somatrogon treatment) in prepubertal children (3 to 11 years and 3 to 12 years in girls and boys, respectively) with GHD in isolation or as part of multiple pituitary hormone deficiency and without previous treatment, from the perspective of the National Health System. The simulation of the economic model ends at the age of 18. The costs of hormones and monitoring were obtained from Spanish sources. The utilities were obtained from the literature. Spanish clinical experts validated the assumptions of the model. Results In the deterministic analysis, somatrogon would be cost-effective, compared to GH-d, with a cost per QALY (quality-adjusted life year) gained of €19,259 and a clinically relevant QALY gain (0.336). This result was confirmed in deterministic sensitivity analyses. According to the probabilistic analysis, somatrogon would be the dominant treatment, with a 61% probability of a willingness to pay of €25,000 per QALY gained. Conclusion Compared to GH-d, somatrogon is cost-effective in the Spanish pediatric population with GHD.