Active transportation (walking or cycling) as a substitute for car trips still represents a small percentage of all daily travels in many European cities. This study aimed to estimate the health and economic co-benefits for the adult population of modal shift from driving to active travel in urban environments. Three scenarios were modelled for the case study, the city of Porto, Portugal, by comparing travel patterns of 2013 to hypothetical scenarios of modal shifts from driving to active transport, namely: i) SC1 - conservative scenario, with a change of 5% from driving to cycling and 10% from driving to walking; ii) SC2 - moderate scenario, with a shift of 10% and 15%, respectively; and iii) SC3 - optimistic scenario, with a shift of 15% and 20%, respectively. The mortality risk reduction for five health outcomes (colon and breast cancers, diabetes, ischemic heart disease, cerebrovascular disease) was assessed, including an estimation of traffic injury and air pollution exposure risks. Results were presented in Disability-Adjusted Life Years (DALYs) avoided. Economic valuation for each scenario was performed using a Willingness-to-Pay approach for morbimortality and a Cost of Illness approach for 2013 hospitalizations and work absenteeism. Significant health benefits were found in all modelled scenarios, ranging from 1657 (16%) to 2881 (28%) DALYs avoided. Total costs averted ranged from €3894 to €6769 million through the scenarios. Cardio and cerebrovascular diseases mortality presented the largest benefit, accounting for about 3/4 of all avoidable DALYs in all scenarios. Reductions in CO2 and PM10 emissions were calculated, showing a decrease from 31.6 to 73.7 kt of CO2 and 7 to 16 t for PM10, respectively. A modal shift towards active transportation could lead to significant health and economic benefits, indicating that the evaluation of health impacts should be included in the analysis of active transport interventions.