Prader-Willi syndrome (PWS), a genetically determined disorder, the most frequent cause of early onset obesity, is associated with physical and cognitive dysfunctions and behavioural disturbances; these disturbances are frequently treated with psychotropic medication. The aim of this cross sectional study was to describe the characteristics of the first large national sample of PWS in Spain and analyse the relationships of those characteristics with key demographic and clinical factors. Participants were recruited among all members of the Spanish PWS Association who agreed to take part in the study and fulfilled its inclusion criteria. Family and patient demographic features, family size and birth order, intelligence quotient, anthropometric measures, lifestyle habits, behavioural disturbances and clinical data, as well as use of psychotropic drugs and their side effects (with the UKU scale), were collected in genetically-confirmed cases of PWS. Bivariate and logistic regression analyses were used for determining the associations of demographic and clinical factors with both obesity and the regular use of psychotropic medication. The cohort included 177 participants (6-48 years), 50.8% males. Behavioural disturbances were present in a range of 75% to 93% of participants; psychotropic medication was prescribed to 81 (45.8%) of them. Number of siblings showed a direct correlation with IQ, especially among males, and inappropriate speech was more intense in only-child females. Obesity was, in parallel, strongly associated with ascending age and with not being currently under growth hormone treatment. Participants taking any psychotropic medication were characterized by more frequent age ≥30, high level of hyperactivity and a psychiatric diagnosis. Conclusion Characterisation of persons with PWS in Spain confirms their physical and behavioural phenotype and supports the long-term application of GH therapy and the rational use of psychotropic medication.