Simple SummaryDirofilariosis (Dirofilariaspp.) is a vector-borne zoonotic disease that mainly affects canids and felids, both domestic and wild, and accidentally humans. In Spain and Portugal, it is considered an endemic disease where the prevalence is not uniform throughout the territory. The objective is to carry out a quantitative proposal of the risk of infection byDirofilariaspp., using as key variables the potential distribution of suitable habitats forCulex pipienscalculated via an ecological niche model (ENM) and the potential number ofDirofilariaspp. generations. In addition, the impact of possible future climatic conditions was estimated to the periods of the 2040s, 2060s, and 2080s. The resulting model was validated with the prevalence and geolocation ofD. immitis-infected dogs from all provinces and districts. The risk ofDirofilariaspp. infection was high throughout the peninsula and the Balearic Islands, with the exception of higher-altitude areas. We found a robust and positive relationship between the risk of dirofilariosis and observed the prevalence of infested dogs in the study area. The territory gain ofCx. pipienswill increase by 49.98%, potentially increasing the risk. This new model increases the accuracy and predictive value of existing models.AbstractDirofilariosis is a vector-borne zoonotic disease whose distribution is linked to the presence of culicid mosquitoes. Spain and Portugal are considered endemic countries; however, the distribution of dirofilariosis is not uniform. Our aim was to develop a more accurate risk model of dirofilariosis transmission for the Iberian Peninsula (Spain and Portugal) and the Balearic Islands (Spain). To do this, we used a set of key variables related to parasite transmission: the potential distribution of suitable habitats forCulex pipienscalculated via an ecological niche model (ENM) and the potential number ofDirofilariaspp. generations. The resulting model was validated with the prevalence and geolocation ofD. immitis-infected dogs from all provinces and districts. In addition, the impact of possible future climatic conditions was estimated. A quantitative estimate of the risk of infection byDirofilariaspp. was obtained at a resolution of 1 km2. The entire analyzed territory was susceptible to contact with the parasite. The highest risk of infection was found throughout the eastern coastal strip and the south of the Iberian Peninsula and the Balearic Islands, as well as in the areas surrounding the basins of the main rivers, and the lowest risk was located in the higher-altitude areas. We found a robust and positive relationship between the risk of dirofilariosis and the observed prevalence of infested dogs in the study area (β ± SE = 3.32 ± 1.43p< 0.05). In 2080, the percentage of territory gain forCx. pipienswill increase to 49.98%, which will increase the risk of infection. This new model provides a high predictive value for the current and predicted presence and risk and can serve as a tool for the management and control of dirofilariosis.