The genetic incompatibility avoidance hypothesis as an explanation for the polyandrous mating strategies (mating with more than one male) of females of many species has received significant attention in recent years. It has received support from both empirical studies and a meta-analysis, which concludes that polyandrous females enjoy increased reproductive success through improved offspring viability relative to monandrous females. In this study we investigate whether polyandrous female Drosophila simulans improve their fitness relative to monandrous females in the face of severe Wolbachia-associated reproductive incompatibilities. We use the results of this study to develop models that test the predictions that Wolbachia should promote polyandry, and that polyandry itself may constrain the spread of Wolbachia. Uniquely, our models allow biologically relevant rates of incompatibility to coevolve with a polyandry modifier allele, which allows us to evaluate the fate of the modifier and that of Wolbachia. Our empirical results reveal that polyandrous females significantly reduce the reproductive costs of Wolbachia, owing to infected males being poor sperm competitors. The models show that this disadvantage in sperm competition can inhibit or prevent the invasion of Wolbachia. However, despite the increased reproductive success obtained by polyandrous females, the spread of a polyandry modifier allele is constrained by any costs that might be associated with polyandry and the low frequency of incompatible matings when Wolbachia has reached a stable equilibrium. Therefore, although incompatibility avoidance may be a benefit of polyandry, our findings do not support the hypothesis that genetic incompatibilities caused by Wolbachia promote the evolution of polyandry.