Purpose. To study and compare the structure of off-label drug use in children in 2012 and 2015 by means of analysis of the national pharmacovigilance database. Materials and methods. We conducted a comparative analysis of 341 spontaneous reports about serious adverse reactions in children, submitted to the Russian pharmacovigilance database in 2012, and 467 suchlike spontaneous reports registered in 2015. Approved in the Russian Federation prescribing drug information was used to identify «off label» drug use. Results. It was established that 58,7% of suspected medicines in 2012 and 47,5% in 2015, the use of which was associated with the development of serious complications in pharmacotherapy in children, were prescribed with deviations from the recommendations of approved prescribing drug information. Systemic antimicrobial agents and drugs for the treatment of nervous system diseases were the most common groups of drugs prescribed off-label in pediatric practice. The main types of off-label violations were inappropriate indications, deviations from the recommended dosage regimen and the use of a drug in the age group of patients, wherein the drug has not been approved. Conclusion. Our research confirms, that the practice of off-label drug use in children is not safe. It is shown that spontaneous reporting is an effective method of study the problems of drug safety in children.