Abstract Many hermaphroditic flowering plants species possess a genetic self-incompatibility (SI) system that prevents self-fertilization and is typically controlled by a single multiallelic locus, the S-locus. The conditions under which SI can be stably maintained in single isolated populations are well known and depend chiefly on the level of inbreeding depression and the number of SI alleles segregating at the S-locus. However, while both the number of SI alleles and the level of inbreeding depression are potentially affected by population subdivision, the conditions for the maintenance of SI in subdivided populations remain to be studied. In this paper, we combine analytical predictions and two different individual-based simulation models to show that population subdivision can severely compromise the maintenance of SI. Under the conditions we explored, this effect is mainly driven by the decrease of the local diversity of SI alleles rather than by a change in the dynamics of inbreeding depression. We discuss the implications of our results for the interpretation of empirical data on the loss of SI in natural populations. Data accessibility statement No data to be archived