Passwords are still the most widespread means for authenticating users, even though they have been shown to create huge security problems. This motivated the use of additional authentication mechanisms in so-called multi-factor authentication protocols. In this article, we define a detailed threat model for this kind of protocol: While in classical protocol analysis attackers control the communication network, we take into account that many communications are performed over TLS channels, that computers may be infected by different kinds of malware, that attackers could perform phishing, and that humans may omit some actions. We formalize this model in the applied pi calculus and perform an extensive analysis and comparison of several widely used protocols—variants of Google 2-step and FIDO’s U2F (Yubico’s Security Key token). The analysis is completely automated, generating systematically all combinations of threat scenarios for each of the protocols and using the P ROVERIF tool for automated protocol analysis. To validate our model and attacks, we demonstrate their feasibility in practice, even though our experiments are run in a laboratory environment. Our analysis highlights weaknesses and strengths of the different protocols. It allows us to suggest several small modifications of the existing protocols that are easy to implement, as well as an extension of Google 2-step that improves security in several threat scenarios.