A new anelastic large-eddy simulation (LES) model with an Eulerian dynamical core and Lagrangian particle-based microphysics is presented. The dynamical core uses the multidimensional positive-definite advection transport algorithm (MPDATA) advection scheme and the generalized conjugate residual pressure solver, whereas the microphysics scheme is based on the super-droplet method. Algorithms for coupling of Lagrangian microphysics with Eulerian dynamics are presented, including spatial and temporal discretizations and a condensation substepping algorithm. The model is free of numerical diffusion in the droplet size spectrum. Activation of droplets is modeled explicitly, making the model less sensitive to local supersaturation maxima than models in which activation is parameterized. Simulations of a drizzling marine stratocumulus give results in agreement with other LES models. It is shown that in the super-droplet method a relatively low number of computational particles is sufficient to obtain correct averaged properties of a cloud, but condensation and collision–coalescence have to be modeled with a time step of the order of 0.1 s. Such short time steps are achieved by substepping, as the model time step is typically around 1 s. Simulations with and without an explicit subgrid-scale turbulence model are compared. Effects of modeling subgrid-scale motion of super-droplets are investigated. The model achieves high computational performance by using graphics processing unit (GPU) accelerators.