Background: By 2050, nearly 70% of the global population is projected to live in urban areas. Because the environments we inhabit affect our health, urban and transport designs that promote healthy living are needed. Objective: We estimated the number of premature deaths preventable under compliance with international exposure recommendations for physical activity (PA), air pollution, noise, heat, and access to green spaces. Methods: We developed and applied the Urban and TranspOrt Planning Health Impact Assessment (UTOPHIA) tool to Barcelona, Spain. Exposure estimates and mortality data were available for 1,357,361 residents. We compared recommended with current exposure levels. We quantified the associations between exposures and mortality and calculated population attributable fractions to estimate the number of premature deaths preventable. We also modeled life-expectancy and economic impacts. Results: We estimated that annually, nearly 20% of mortality could be prevented if international recommendations for performance of PA; exposure to air pollution, noise, and heat; and access to green space were followed. Estimations showed that the greatest portion of preventable deaths was attributable to increases in PA, followed by reductions of exposure to air pollution, traffic noise, and heat. Access to green spaces had smaller effects on mortality. Compliance was estimated to increase the average life expectancy by 360 (95% CI: 219, 493) days and result in economic savings of 9.3 (95% CI: 4.9, 13.2) billion EUR/year. Conclusions: PA factors and environmental exposures can be modified by changes in urban and transport planning. We emphasize the need for a) the reduction of motorized traffic through the promotion of active and public transport and b) the provision of green infrastructure, both of which are suggested to provide opportunities for PA and for mitigation of air pollution, noise, and heat.