We conducted a mesocosm restoration experiment to test the efficacy of early summer sowing of seed mixtures for inhibiting the emergence, growth and/or survival of giant hogweed (Heracleum mantegazzianum) seedlings. H. mantegazzianum is invasive in Europe and North America, where it has a negative effect on plant diversity and represents a serious health hazard, due to the photodermatitis it may cause. We tested five plant mixtures comprising a selection of North American native or naturalized non-invasive plant species. Compared to the unseeded control mesocosm, all plant covers reduced seedling emergence, growth and survival of H. mantegazzianum. There were large differences between mixtures regarding inhibition effects. The nature of the effects depended on species composition, with one mixture more effective in preventing establishment, another essentially affecting seedling growth and survival. Total plant cover, irrespective of seed mixtures, appeared to have a major effect on H. mantegazzianum. Other factors that may have played a role included the litter from the seeded plants and the allelopathic effect of Canada goldenrod (Solidago canadensis). Our study adds to the growing body of evidence promoting the restoration of a plant cover as a means to prevent reinfestation by invasive species following a control operation.