The “setting-less” protection approach is an innovative protection scheme with increased dependability and security. This method is based on dynamic state estimation, which continuously extracts the operating condition of a protection zone from real-time measurements and the protection zone dynamic model. The dynamic state estimation computes the probability that the measurements fit the dynamic model of the protection zone within the measurement accuracy via the Chi-square test. The probability represents the goodness of fit of measurements to the dynamic model of the protection zone. We refer to it as the confidence level that the protection zone is healthy. High confidence levels imply that the protection zone operates normally, while low confidence levels indicate that internal abnormalities/faults may have occurred. Note that the proposed method does not require coordination with other protection schemes which sometimes compromise security and/or dependability. In this paper, the setting-less protection approach is described and applied to transformer protection. The feasibility of the setting-less transformer protection is verified with numerical experiments of several case studies (e.g., transformer energization, external faults, internal faults, and high impedance faults). The method has been verified in the laboratory and there are plans for field testing.