<p>Constructing mechanistic explanations that link subatomic entities and activities to molecular behaviours and chemical reactions is at the heart of organic chemistry. This means organic chemistry offers a rich context for supporting learners in developing robust causal mechanistic schema and epistemic criteria for explanations. However, undergraduate organic chemistry students’ epistemic cognition, or knowledge for constructing and evaluating explanations, has yet to be explored. Therefore, this article presents findings from a study of students’ epistemic criteria for explanations in an organic chemistry context. A task that presented students with an unexpected phenomenon and four possible explanations was administered electronically to a large-enrolment, second-year undergraduate organic chemistry class. The data collected were students’ written justifications for selecting the explanation they believe best explained the phenomenon and eliminating alternative explanations. Thematic analysis of these justifications revealed many epistemic criteria—including ideas about language, reasoning, and familiarity—that students used to evaluate the explanations. The findings reveal the ways these criteria were used to navigate multiple explanations. For instance, some students chose less mechanistic explanations based on alignment with more familiar classroom language and ideas, whereas others prioritized explanatory depth over a sense of familiarity. Findings from this study have implications for supporting postsecondary science students’ epistemic cognition and conceptual learning of reaction mechanisms.</p>