For the past sixty years, the industrial complex in Lacq (Pyrénées-Atlantiques) has been home to numerous chemical and petrochemical operations. To assess their health impacts on nearby residents, in response to a request in October 2015 from the Ministry of Health, Santé publique France launched a series of health studies to estimate health risks, including mortality—a topic on which a separate study had been conducted in 2001. The mortality study presented in this report relied on two analytical strategies to assess potential excess mortality among residents of the Lacq area compared to the Aquitaine population, and within the most exposed area compared to less exposed areas. The first strategy (Strategy No. 1) was based on the same method as that of the 2001 study (98 municipalities divided into a nearby residential zone and two more distant comparison zones) covering the period from 1968 to 2014. The second strategy (Strategy No. 2) took into account industrial changes since 2001 and exposure data from the most recent area-level risk assessments. These data, combined with expert opinion, enabled a refined classification of the study area into three zones comprising 99 municipalities: Zone A comprising the residential municipalities considered most exposed, Zone B with intermediate exposure, and Zone C with the lowest exposure. Strategy No. 2 relied on a multivariate model, whose analyses also accounted for several potential confounding factors, such as the aggregate socioeconomic status at the municipal level, and covered a more recent study period (1999–2014). Comparative mortality indices (CMI) were calculated using indirect standardization based on mortality rates in the Aquitaine region, providing estimates both overall and by age group, sex, and cause of death across different calendar periods. Regardless of the analysis strategy, there was no excess risk of death for all causes of death, all cancer deaths, deaths from respiratory cancers, deaths from lymphoid tissue cancers, or deaths from digestive cancers in the nearest residential areas. However, using analysis strategy No. 1, an excess mortality from non-cancerous respiratory diseases was observed between 1968 and 2014 for the population residing in the closest zone and the population residing in the intermediate exposure zone. Analysis strategy No. 2 showed excess risks of death from non-cancerous diseases of the respiratory and circulatory systems for the population residing in the intermediate exposure zone over the 1999–2014 period. These excess risks are not directly associated with residential exposure to the industrial zone, regardless of the analysis strategy used. Furthermore, Strategy No. 2 showed a significant under-mortality for all cancers in the nearest residential zone. When all causes of death are considered, the analyses for the period in question do not show excess mortality in the study area population compared to the population of Aquitaine. When considering the risk of death by specific cause, excesses are observed for non-cancerous respiratory and circulatory diseases, and a lower risk for all-cancer deaths, even after accounting for certain potential confounding factors at an aggregate level. These results raise hypotheses regarding differences between areas based on occupational exposures, resident mobility, or healthcare utilization, which could be taken into account in the participatory health survey. The morbidity survey in the Lacq area will also allow for the exploration of these two health indicators.