Work interruptions are contemporary job stressors that occur frequently in the workplace. Theories on work interruptions and the stressor–strain relationship over time suggest that work interruptions should have a lagged negative effect on well-being. However, we argue that continued changes in work interruptions may also be important for employees’ well- being. We investigated the mid- and long-term effects of work interruptions on employee job satisfaction and psychosomatic complaints across two studies (Study 1: N = 415, four waves over five years; Study 2: N = 663, five waves over eight months). Using latent growth modeling, we predicted job satisfaction and psychosomatic complaints with respect to the level of, and changes in, interruptions. Controlling for initial well-being, we found that the mean levels (intercepts) of work interruptions had negative effects on later well-being in Study 1, but not in Study 2. However, increases in interruptions over time (slopes) predicted later well-being consistently. An analysis on reversed effects revealed that only the initial level of psychosomatic complaints positively predicted work interruptions. The studies underscore not only the importance of interruptions for well-being over time in general, but also the particular importance of increases in interruptions.