Introduction The area around Brindisi (Apulia region) is characterized by three thermoelectric power plants established in different time periods (1961, 1969, and 1991), two of which remain active. These plants vary in terms of combustible material (oil and coal) and pollution control technology. The study aimed to evaluate the effects of emissions from the power plants on mortality in a cohort of people living in the area, taking into account the effect of socioeconomic position (SEP) and other contextual variables. Methods A cohort of residents from 2000 to 2013 were enrolled from Municipal Registers and followed until 2013. Individual data were linked with the regional mortality register. Census data from 2001 at census block level were used to assess an area-based SEP index. Exposure to power plants emissions in 1998 (PM10 as tracer) at each residential address was estimated using Lagrangian dispersion models. Cox mortality Hazard Ratios were calculated including a linear term for industrial PM10 exposure (95th-5th percentiles difference), age, gender, calendar period, and SEP (HRs, 95%CI). Results A total of 223,934 people were enrolled (48% male, 40% low SEP). The annual average population exposure levels [mean (SD, 50th percentile, 95th-5th percentile)] of industrial PM10 were 0.30 µg/m3 (0.25, 0.33, 0.62). For increases of PM10 equal to the difference between 95th-5th percentile, we found increasing risks for cancer mortality (HR 1.08, 95%CI 1.04-1.13), pancreatic (HR 1.11, 95%CI 1.01-1.23) and bladder cancers (HR 1.16, 95%CI 1.04-1.30), respiratory disease (HR 1.12, 95%CI 1.03-1.22), and acute coronary events (HR 1.11, 95%CI 1.00-1.23). Conclusions Industrial pollution from power plants was associated with cohort mortality of the people resident in the area. The effect estimates are large although there are uncertainties in the retrospective estimation of the absolute concentrations of industrial pollutants.