The urban structure is the main determinant of population exposure to a number of environmental factors. Several aspects of urban life, including increased exposure to air pollution (AP), traffic noise, and lack of green areas can have detrimental effects on health and may contribute to increased morbidity and premature mortality. We aimed to estimate the health impact of AP, traffic noise, and lack of green on residents in Rome. Annual PM2.5 concentrations in 2015 (1km x 1km grid) were estimated using the FARM dispersion model developed by the Lazio Regional Environmental Agency; road traffic noise indicators (Lden, LAeq16h, Lnight) were estimated at census tract level using the acoustic model Sound Plan 7.4 (reference to 2009 traffic flow data); ArcMap was used to assess the percentage of residential addresses with a green area within 300m. For PM2.5 and NO2 we estimated attributable premature deaths from natural causes and lung cancer, and incidence of coronary events. Non-accidental premature deaths attributable to lack of green areas were also estimated for 1,926,736 residents within ring road area. For noise we estimated attributable cases of non-accidental mortality, hypertension, sleep disorders and incidence of coronary events. Available exposure-response functions (WHO/HRAPIE and updates for AP; published meta-analytic estimates for noise and green) were used. The counterfactual levels used were 10ug/m3 for PM2.5, 5dB(A) for Lden and LAeq16h, 40 dB(A) for Lnight, and 100% of residential addresses without green areas within 300m. 2,617,175 Rome residents are exposed to relatively high mean annual levels of PM2.5 (18.6 ug/m3). The noise mean exposure levels are also high, 60.5 dB(A) Lden, 62.6 dB(A) LAeq16h, and 51.3 dB(A) Lnight. 50% of residential addresses have lack of green within 300 m. We estimated 1,526 (CI95% 896-1928) annual premature deaths, 960 incident coronary events and 148 lung cancer deaths attributable to PM2.5. A total of 882 (CI95% 78-1,487) annual premature deaths, 15,458 (CI95% 5,277-24,491) hypertension cases, 247 (CI95% 129-383) incident coronary events, and 146,744 (CI95% 76,187-261,099) sleep disorders are attributable to traffic noise. 979 premature deaths were attributable to lack of green areas. The HIA indicates an important negative impact of air pollution, noise and lack of green areas in the city of Rome. The results call for the adoption of radicals interventions in order to reduce vehicular traffic in the city (especially diesel vehicles) and increase greenness to reduce population exposure and prevent large health effects.