Population models can be a useful tool for ecological risk assessment to increase ecological realism. In the present study, population models were used to extrapolate toxicity test results of four metals (Ag, Cu, Ni, Zn) to the population level. In total, three primary producers, five invertebrate species, and five fish species were covered. The ecological modeling–based laboratory to population effect extrapolation factor (ECOPEX factor), defined as the ratio of the predicted 10% effect concentration (EC10) at the population level and the observed EC10 for the laboratory toxicity test, ranged from 0.7 to 78.6, with a median of 2.8 (n = 27). Population modeling indicated clearly higher effect concentrations in most of the cases (ECOPEX factor >2 in 14 out of 27 cases), but in some cases the opposite was observed (in three out of 27 cases). We identified five main contributors to the variability in ECOPEX factors: (1) uncertainty about the toxicity model, (2) uncertainty about the toxicity mechanism of the metal, (3) uncertainty caused by test design, (4) impact of environmental factors, and (5) impact of population endpoint chosen. Part of the uncertainty results from a lack of proper calibration data. Nonetheless, extrapolation with population models typically reduced the variability in EC10 values between tests. To explore the applicability of population models in a regulatory context, we included population extrapolations in a species sensitivity distribution for Cu, which increased the hazardous concentration for 5% of species by a factor 1.5 to 2. Furthermore, we applied a fish population model in a hypothetical Water Framework Directive case using monitored Zn concentrations. This article includes recommendations for further use of population models in (metal) risk assessment. Environ Toxicol Chem 2024;43:2308–2328. © 2024 SETAC