Abstract The distributed permutation flowshop scheduling problem (DPFSP) has attracted a lot of attention in recent years, as current production systems frequently operate multiple factories at once. Due to the practical relevance of mixed no-idle flowshop, we address an extension of the DPFSP where there are identical factories, each one with a mixed no-idle flowshop environment. In a mixed no-idle flowshop regular machines exist side-by-side with stages that require a non-stop process. The addressed problem also takes into account sequence-dependent setup times on conventional machines. To the extent of our knowledge, this issue has not yet been examined in the literature despite it can be encountered in current manufacturing systems. For the purpose, we present a MILP formulation, a novel constructive heuristic and iterated greedy algorithms. A new construction scheme based on inter-factory and intra-factory improvement schemes is provided for the novel heuristic to further improve the solution quality given by the method. For the iterated greedy algorithm, we developed a new efficient reconstruction strategy to enhance the exploration capability of the algorithm. Furthermore, a large new benchmark was generated using a well recognized set of instances. The state-of-the-art methods and our proposed algorithms were tested in an extensive statistical and computational experiment. The analysis show that our proposals outperformed the methods from the literature.