Inability to engage with positive stimuli is a widespread problem associated with negative mood states across many conditions, from low self-esteem to anhedonic depression. Though attention retraining procedures have shown promise as interventions in some clinical populations, novel procedures may be necessary to reliably attenuate chronic negative mood in refractory clinical populations (e.g., clinical depression) through, for example, more active, adaptive learning processes. In addition, a focus on individual difference variables predicting intervention outcome may improve the ability to provide such targeted interventions efficiently. To provide preliminary proof-of-principle, we tested a novel paradigm using operant conditioning to train eye gaze patterns toward happy faces. Thirty-two healthy undergraduates were randomized to receive operant conditioning of eye gaze toward happy faces (train−happy) or neutral faces (train−neutral). At the group level, the train−happy condition attenuated sad mood increases following a stressful task, in comparison to train−neutral. In individual differences analysis, greater physiological reactivity (pupil dilation) in response to happy faces (during an emotional face-search task at baseline) predicted decreased mood reactivity after stress. These Preliminary results suggest that operant conditioning of eye gaze toward happy faces buffers against stress-induced effects on mood, particularly in individuals who show sufficient baseline neural engagement with happy faces. Eye gaze patterns to emotional face arrays may have a causal relationship with mood reactivity. Personalized medicine research in depression may benefit from novel cognitive training paradigms that shape eye gaze patterns through feedback. Baseline neural function (pupil dilation) may be a key mechanism, aiding in iterative refinement of this approach. (PsycINFO Database Record (c) 2016 APA, all rights reserved)