Understanding and evaluating the factors that influence the persistence of small populations and establishment of new populations are basic goals of conservation biology. Genetic effects due to genetic drift and inbreeding can have important impacts on the success of new populations. Many bighorn sheep populations in western North America have had low numbers and many have gone extinct. Here, the possible effects of genetic drift and inbreeding are evaluated in three populations of desert bighorn sheep initiated in the 1970s from translocations. One of these has no molecular genetic data but has substantial demographic data (Aravaipa Canyon), one has both extensive demographic data and some molecular genetic data (Red Rock), and one has limited demographic data and some molecular genetic data (Tiburon Island). Overall, either from theoretical pedigree analysis and population genetic estimates from demographic history (Aravaipa, Tiburon) or from molecular data (Red Rock, Tiburon), it appears that the levels of genetic drift and inbreeding are substantial in all of these populations. This impact was larger when higher variance in male reproductive success was assumed. In other words, it appears that genetic factors are and will be important in the establishment and persistence of these populations. These examples in long-term monitored bighorn sheep populations are relevant to many endangered species in similar situations where demographic data are available but there is little or no historical molecular genetic data.