Pag. R4-1 t/m R4-11 Abstract: The breakup of droplets due to creeping motion in a confined microchannel geometry is studied using three-dimensional numerical simulations. Analogously to unconfined droplets, there exist two distinct breakup phases: (i) a quasi-steady droplet deformation driven by the externally applied flow; and (ii) a surface-tension-driven three-dimensional rapid pinching that is independent of the externally applied flow. In the first phase, the droplet relaxes back to its original shape if the externally applied flow stops; if the second phase is reached, the droplet will always break. Also analogously to unconfined droplets, there exist two distinct critical conditions: (i) one that determines whether the droplet reaches the second phase and breaks, or it reaches a steady shape and does not break; and (ii) one that determines when the rapid autonomous pinching starts. We analyse the second phase using stop-flow simulations, which reveal that the mechanism responsible for the autonomous breakup is similar to the end-pinching mechanism for unconfined droplets reported in the literature: the rapid pinching starts when, in the channel mid-plane, the curvature at the neck becomes larger than the curvature everywhere else. The same critical condition is observed in simulations in which we do not stop the flow: the breakup dynamics and the neck thickness corresponding to the crossover of curvatures are similar in both cases. This critical neck thickness depends strongly on the aspect ratio, and, unlike unconfined flows, depends only weakly on the capillary number and the viscosity contrast between the fluids inside and outside the droplet.