The impact of climate trends during the period 1901-2009 on the life cycle of Hyalomma marginatum in Europe was modeled to assess changes in the physiological processes of this threat to public health. Monthly records of temperature and water vapour at a resolution of 0.5° and equations describing the life cycle processes of the tick were used. The climate in the target region affected the rates of the life cycle processes of H. marginatum: development rates increased, mortality rates in molting stages decreased, and the survival rates of questing ticks decreased in wide territories of the Mediterranean basin. The modeling framework indicated the existence of critical areas in the Balkans, central Europe, and the western coast of France, where the physiological processes of the tick improved to extents that are consistent with the persistence of populations if introduced. A spatially explicit risk assessment was performed to detect candidate areas where active surveys should be performed to monitor changes in tick density or persistence after a hypothetical introduction. We detected areas where the critical abiotic (climate) and biotic (host density) factors overlap, including most of the Iberian peninsula, the Mediterranean coast of France, eastern Turkey, and portions of the western Black Sea region. Wild ungulate densities are unavailable for large regions of the territory, a factor that might affect the outcome of the study. The risk of successfully establishing H. marginatum populations at northern latitudes of its current colonization range seems to be still low, even if the climate has improved the performance of the tick in these areas. ; Parts of this work were supported by EU FP7 ANTIGONE (Anticipating the Global Onset of Novel Epidemics) project number 278976. Parts of this work were conducted in the framework of the EurNegVec (European Neglected Vectors) COST Action TD1303. Climate data were obtained from the Climatic Research Unit, University of East Anglia (United Kingdom). ; Peer Reviewed