At the Asl Napoli 3 SUD a local, regional and national level analysis of prescription and spending related to the prescription and dispensing of drugs intended to increase vitamin D levels in the human body was carried out. The Italian Pharmacy Regulatory Agency (AIFA) in late 2019 introduced a prescriptive note of appropriateness (note 96) to regulate the prescribing activity of a drug that is widely used on the Italian national population, significantly affecting spending by the National Health System (NHS). Despite this action there has been an increase in prescription and expenditure of calcifediol at all levels of analysis (national, regional and local) while regarding the remaining Anatomical Therapeutic Chemical (ATC) referring to drugs used as vitamin D supplement in the Campania Region and at the Asl Napoli 3 SUD there is a slower decrease in expenditure and prescription, sometimes even increasing and in countertendency to the Italian national average. For these reasons, the Campania Region instituted two executive decrees (DD 405/2021 and 91/2022) that led to a marked reduction in spending and prescription in 2022 even higher than in other Italian regional realities. This analysis aims to show how vitamin D prescription is widespread and often inappropriate, attested by wide regional variability. In addition, the main recommendations for the use of these drugs are highlighted in order to raise awareness among all healthcare professionals of the informed use of these molecules ensuring sustainability and governance.