Sequential diagnosis methods compute a series of queries for discriminating between diagnoses. Queries are answered by probing such that eventually the set of faults is identified. The computation of queries is based on the generation of a set of most probable diagnoses. However, in diagnosis problem instances where the number of minimal diagnoses and their cardinality is high, even the generation of a set of minimum cardinality diagnoses is unfeasible with the standard conflict-based approach. In this paper we propose to base sequential diagnosis on the computation of some set of minimal diagnoses using the direct diagnosis method, which requires less consistency checks to find a minimal diagnosis than the standard approach. We study the application of this direct method to high cardinality faults in knowledge-bases. In particular, our evaluation shows that the direct method results in almost the same number of queries for cases when the standard approach is applicable. However, for the cases when the standard approach is not applicable, sequential diagnosis based on the direct method is able to locate the faults correctly.