OBJECTIVE: To determine the incidence rate and mortality of community-acquired pneumonia (CAP) in adults in three cities in Latin America during a three-year period. DESIGN: Prospective population based study. SETTING: Healthcare facilities (outpatient centers and hospitals) in the cities of General Roca (Argentina), Rivera (Uruguay) and Concepcion (Paraguay). PARTICIPANTS: 2302 adults aged 18 years and older with CAP were prospectively enrolled between January 2012 and March 2015. MAIN OUTCOME MEASURES: Incidence rate of CAP in adults, predisposing conditions for disease, mortality at 14 days and at one year were estimated. Incidence rate of CAP, within each age group, was calculated by dividing the number of cases by the person-years of disease-free exposure time based on the last census; incidence rates were expressed per 1000 person-years. RESULTS: Median age of participants was 66 years, 46.44 % were men, 68% were hospitalized. Annual incidence rate was 7.03 (CI95% 6.64-7.44) per 1000 person-years in General Roca, 6.33 (CI95% 5.92-6.78) per 1000 person-years in Rivera and 1.76 (CI95% 1.55-2.00) per 1000 person-years in Concepcion. Incidence rates were highest in participants aged over 65 years. 82.4% had at least one predisposing condition and 48% had 2 or more (multi-morbidity). Chronic heart disease (43.6%) and smoking (37.3%) were the most common risk factors. 14-day mortality rate was 12.1% and one-year mortality was 24.9%. Multi-morbidity was associated with an increased risk of death at 14 days (OR 2.91; 2.23 to 3.80) and at 1 year (OR 3.00; 2.44 to 3.70). CONCLUSIONS: We found a high incidence rate of CAP in adults, ranging from 1.76 to 7.03 per 1000 person-years, in three cities in South America, disclosing the high burden of disease in the region. Efforts to improve prevention strategies are needed.