Declines in populations of many species across the United States are prompting the need for monitoring programs that can detect population change effectively for large suites of species. The proliferation of reliable standardized monitoring techniques enhances the potential that we may meet these burgeoning information needs. However, multiple-species monitoring approaches are still a rarity. In an attempt to meet monitoring information needs on National Forest System (NFS) lands, the U.S. Forest Service developed the Multiple Species Inventory and Monitoring (MSIM) protocol, an approach that employs a variety of vertebrate and habitat survey methods to obtain presence–absence data for a broad spectrum of species at a systematic array of sample points throughout ecoregions. A recent evaluation of the MSIM protocol predicted that its implementation across the Sierra Nevada ecoregion would detect a 20% change in proportion of points occupied for 76% of the species with 80% confidence and power. This evaluation was based on a qualitative estimate of probability of detection and basic habitat association information to estimate probability of presence. We conducted a field test to evaluate the ability of a multi-taxonomic, presence–absence monitoring approach to detect and estimate population change at multiple scales and to meet the monitoring needs of land management agencies. Our field data consisted of bird, mammal, amphibian, and reptile surveys conducted at terrestrial and aquatic sites in the Lake Tahoe basin, located in the central Sierra Nevada. We used a maximum likelihood function to quantitatively estimate the probability of detection and sampling adequacy of species and species groups. We compared these observed estimates to the previously derived expected estimates. We detected 185 species by field testing, including 89% of the expected species and several species that were not expected. Observed probabilities of detection were generally lower than we expected. Sampling adequacy was also lower than we expected but still relatively high, with 66% of the Lake Tahoe species and 47% of all Sierra Nevada species adequately sampled. Species with small geographic ranges, narrow habitat specificity, or small population sizes were considered rare, and they were not sampled as adequately as other species groups. Still, 69 of the rarest species, including 12 species with state or federal designation as endangered, threatened, or sensitive, were estimated to be adequately sampled. Our analysis highlighted the ability of a broad-scale, multi-taxonomic presence–absence monitoring approach, such as the MSIM protocol, to detect population change for a large number and wide variety of vertebrate species. The outcome of our test also suggests that many data yields would be garnered at the scale of National Forests and National Parks, such as distribution and occurrence data for most species, including little-known species, population trend data for many species, habitat relationships and habitat condition data, and data on association strengths of indicator species.