Non-interventional studies (NIS) are of particular interest over the past decade in Russia. However, absence of legal regulations including the matters of quality assurance is still one of the fundamental problems. The objective of this article is actualizing the problem of quality assurance in NISs. The authors discuss a systematic approach to development and implementation of key aspects of NIS quality assurance considering the features of NISs in comparison with clinical trials. The problem of quality assurance is considered at all levels of NIS organization: strategic (development of quality management system, risk-based monitoring strategy), tactical (implementation of risk-based monitoring concept in real research practice) and operational (specifics of on-site monitoring, remote monitoring). The key principles of Quality Management System development for NISs as well as the features of NISs affecting the processes of quality assurance and control are considered in this article. The concept of risk-based monitoring and development of a monitoring plan as one of the key plans in NIS quality assurance are of particular attention. On-site monitoring in NISs has certain features. In particular, the most difficult stage is a process of source document verification. Therefore, knowledge about problems at this stage are systematized in the article. An important role in risk-based monitoring is assigned to centralized monitoring (remote and based on statistical methods). It is concluded that quality risk management approach is an important aspect of NIS realization. Systematic approach to quality assurance is an important step not only to improve NIS quality in Russia, but also lays the foundation for quality assurance development in real-world studies.