Meditation apps are the most widely used mental health apps. The precise mechanisms underlying their effects remain unclear. In particular, the degree to which affect experienced during meditation is associated with outcomes has not been established. We used the meditation app arm of a recently completed randomized controlled trial comparing a self-guided meditation app (Healthy Minds Program) to a waitlist control. Predominantly distressed public school employees (n = 243, 80.9% with clinically elevated depression and/or anxiety) reported positive and negative affect during meditation practice. Data were analyzed using two-level multivariate latent growth curve models (observations nested within participants) that simultaneously attended to both positive and negative affect. We examined whether positive and negative affect during meditation changed over time and whether these changes were associated with changes in psychological distress (parent trial's preregistered primary outcome) at posttest or 3-month follow-up. On average, participants reported decreased negative affect but no change in positive affect during meditation over time. Increased positive affect and decreased negative affect during meditation were associated with improvements in distress at posttest and follow-up. Change in positive affect was a stronger predictor of distress at follow-up than change in negative affect. Despite notions embedded within mainstream mindfulness meditation training that deemphasize the importance of the affective experience of practice (i.e., nonjudgmental awareness of present moment experience, regardless of valence), results indicate that these experiences contain signals associated with outcomes. Monitoring affect during meditation may be worthwhile to guide intervention delivery (i.e., measurement-based care, precision medicine). (PsycInfo Database Record (c) 2024 APA, all rights reserved).