This article concerns the scientific value of the theory of autopoietic systems as developed by Maturana and Varela. In a first step, the explanatory power of the theory is investigated. It is argued that, due to the tautological nature of its core concept and the absence of the specification of the organization of the autopoietic system, the empirical counterparts of the theory’s constructs cannot be determined. This renders the theory inadequate for descriptive and explanatory purposes. Proponents of autopoietic system theory do not agree with this kind of reasoning and its conclusion, since autopoietic systems, in their view, cannot be observed precisely because of its autopoietic nature. In a subsequent step, therefore, the epistemology advocated by Maturana and Varela on which this counter argument rests is discussed. It is shown that the interpretation of the ultrastable system, which underlies this epistemology, is not correct. Consequently, it is concluded that autopoietic system theory as developed by Maturana and Varela is unscientific.