Hermaphroditic plants can potentially self-fertilise, but most possess adaptations that promote outcrossing. However, evolutionary transitions to higher selfing rates are frequent. Selfing comes with a transmission advantage over outcrossing, but self-progeny may suffer from inbreeding depression, which forms the main barrier to the evolution of higher selfing rates. Here, we assessed inbreeding depression in the North American herb Arabidopsis lyrata, which is normally self-incompatible, with a low frequency of self-compatible plants. However, a few populations have become fixed for self-compatibility and have high selfing rates. Under greenhouse conditions, we estimated mean inbreeding depression per seed (based on cumulative vegetative performance calculated as the product of germination, survival and aboveground biomass) to be 0.34 for six outcrossing populations, and 0.26 for five selfing populations. Exposing plants to drought and inducing defenses with jasmonic acid did not magnify these estimates. For outcrossing populations, however, inbreeding depression per seed may underestimate true levels of inbreeding depression, because self-incompatible plants showed strong reductions in seed set after (enforced) selfing. Inbreeding-depression estimates incorporating seed set averaged 0.63 for outcrossing populations (compared to 0.30 for selfing populations). However, this is likely an overestimate because exposing plants to 5% CO2 to circumvent self-incompatibility to produce selfed seed might leave residual effects of self-incompatibility that contribute to reduced seed set. Nevertheless, our estimates of inbreeding depression were clearly lower than previous estimates based on the same performance traits in outcrossing European populations of A. lyrata, which may help explain why selfing could evolve in North American A. lyrata.