OBJECTIVES:  Autosomal dominant polycystic kidney disease (ADPKD) affects 3.96/10,000 population in Europe and is the leading inheritable cause of end-stage renal disease (ESRD). Robust models of ADPKD progression, characterised by increased total kidney volume (TKV) and declining renal function, are important to inform patient management and treatment decisions. This study aimed to assess the validity of the ADPKD Outcomes Model (ADPKD-OM) from a Spanish perspective and evaluate the impact of slowing disease progression via treatment in terms of ESRD incidence and renal replacement therapy (RRT) requirements. METHODS:  The ADPKD-OM is a patient-level lifetime simulation relating baseline and time-dependent age, TKV and estimated glomerular filtration rate to ESRD. The model’s clinical face and operational validity were assessed by external Spanish experts (clinical/modelling). Life expectancy, ESRD incidence and time on RRT were predicted for patients with/without tolvaptan therapy. Published Spanish data informed ESRD model inputs; patient characteristics and treatment effect on renal function decline (31.6% reduction) were taken from the TEMPO3:4 study. RESULTS: The validation exercise concluded the model adequately estimated ADPKD disease progression and further highlighted the historically limited availability of TKV in clinical practice and differences in patterns of organ availability and dialysis in Spain. The model estimated 95% of TEMPO3:4 patients reached ESRD at mean age 53 years and spent six years on dialysis, with one transplant performed for every 2–3 patients. Treatment was estimated to prevent 4% of ESRD cases, delay mean time to ESRD by 4.5 years, avoid 5% of transplants, and reduce dialysis time by five months per patient. CONCLUSIONS: The validation of the ADPKD-OM supports the model’s use to inform health outcomes decision-making in Spain. This study indicates that treatment that slows ADPKD progression may alleviate the burden of ESRD for patients and offer meaningful reductions in healthcare resource use, with positive implications for service delivery in Spain.