Hybridization between rare and common congeners poses a recurring challenge in ecological restoration, particularly where multiple conservation priorities overlap. In Pacific Northwest prairies, restoration efforts have brought the federally listed plant Castilleja levisecta into close proximity with C. hispida, a more common congener widely planted to support the endangered Taylor’s checkerspot butterfly (Euphydryas editha taylori). Concerns have emerged that hybridization could compromise the genetic integrity of C. levisecta, yet the strength of reproductive barriers—particularly across cytotypes of C. hispida—has not been quantified. We conducted a controlled greenhouse crossing experiment to evaluate post-pollination reproductive barriers between diploid C. levisecta and diploid, tetraploid, and hexaploid cytotypes of C. hispida. We quantified fruit set, seed set, and germination across reciprocal F1 crosses, assessed fertility of early-generation hybrids through backcrosses and conspecific hybrid crosses, and integrated these components into estimates of overall postzygotic reproductive isolation. Homoploid crosses between diploid C. levisecta and diploid C. hispida produced viable, partially fertile offspring with low reproductive isolation. In contrast, interploid crosses involving tetraploid or hexaploid C. hispida exhibited sharply reduced seed set and germination, resulting in strong to nearly complete isolation. Backcrosses involving diploid hybrids showed little isolation, whereas those involving triploid hybrids were largely infertile. These results indicate that ploidy is a key determinant of postzygotic isolation in this system and suggest that polyploid C. hispida cytotypes represent lower-risk options where co-planting is being evaluated. However, field studies assessing premating barriers and hybrid establishment remain essential for site-specific restoration decisions.