Research has recently started to examine relationships between proactive behavior and employee well-being. Investigating these relationships is important to understand the effects of proactive behavior at work, and whether proactive behavior leads to an increase or a decrease in well- being. In this daily-diary study, we investigated effects of proactive behavior on within-day changes in four indicators of occupational well-being (i.e., activated positive and negative affect, emotional work engagement and fatigue). Moreover, based on the meta-concept of wise proactivity, which suggests that proactive behavior may lead to either favorable or unfavorable consequences depending on certain boundary conditions, we examined organizational tenure and emotion regulation skills as moderators of these effects. In total, N = 71 employees participated in a daily-diary study with two measurements per day for ten consecutive working days. Results showed that emotion regulation skills interacted with proactive behavior to predict within-day changes in emotional work fatigue, such that the effect of proactive behavior on emotional work fatigue was only positive for employees with low (vs. high) emotion regulation skills. Supplementary analyses examining reverse effects of occupational well-being on proactive behavior showed that organizational tenure interacted with activated positive and negative affect in predicting within-day changes in proactive behavior. For employees with lower (vs. higher) organizational tenure, both activated positive and negative affect were negatively associated with proactive behavior. Overall, our findings contribute to the growing body of research on proactive behavior and well-being by demonstrating reciprocal and conditional day-level relationships among these variables.