People strongly differ in their emotional reactions to potentially stressing and challenging environmental circumstances. Two classes of individual differences have independently been reported to contribute to such emotional vulnerability: an attentional bias to negative information and a variation in the serotonin transporter gene (5-HTTLPR). The present study was conducted to investigate the possibility that these cognitive and genetic markers interact in their prospective prediction of emotional reactivity to an extended and mild potential stressor. Changes in dysphoria and anxiety across their first university semester were measured in 120 students. Results indicate that attentional bias toward negative information on Week 1 of the semester significantly predicted cross-semester changes in both anxiety and dysphoria. For the latter, this predictive capacity depended on the 5-HTTLPR genotype. Specifically, only in homozygous carriers of the 5-HTTLPR short allele did attentional bias to negative information on Week 1 significantly predict cross-semester change in dysphoria. These results carry important theoretical and practical implications concerning the ability to identify individuals vulnerable to experiencing elevated emotional reactivity to potentially stressing life-events.