This paper aimed to assess whether differences in the way to conceive happiness, measured by the Orientations to Happiness measure, were associated with specific reactions to negative events. We hypothesized that among orientations to pleasure (portraying hedonism), to meaning (representing a eudaimonic approach to life), and to engagement (derived from the experience of flow), orientation to meaning would have displayed a stronger protective role against recent negative and potentially stressful events. After providing a validation of the Italian version of the Orientations to Happiness measure (Study 1), we performed regression analyses of the three orientations on positive and negative emotions linked to a self-relevant negative event (Study 2), and moderation analyses assessing the interactive effects of orientations to happiness and stressful events on well-being indicators (Study 3). Our findings supported the hypotheses. In Study 2, meaning was associated with positive emotions characterized by a lower activation (contentment and interest) compared to the positive emotions associated with pleasure (amusement, eagerness, and happiness). In Study 3, only meaning buffered the effect of recent potentially stressful events on satisfaction with life and positive affect. Results suggest that orientation to meaning might help individuals to better react to negative events.