The effect of wastewater irrigation on the diversity and composition of bacterial communities of soil mesocosms planted with lettuces was studied over an experiment made of five cultivation campaigns. A limited effect of irrigation with either raw or treated wastewater was observed in both alpha-diversity and beta-diversity of soil bacterial communities. However, the irrigation with wastewater fortified with a complex mixture of fourteen relevant chemicals at 10 mu g/L each, including pharmaceutical, biocide, and pesticide active substances, led to a drift in the composition of soil bacterial community. One hundred operational taxonomic units (OTUs) were identified as responsible for changes between treated and fortified wastewater irrigation treatments. Our findings indicate that under a realistic agronomical scenario, the irrigation of vegetables with domestic (treated or raw) wastewater has no effect on soil bacterial communities. Nevertheless, under the worst-case scenario tested here (i.e., wastewater fortified with a mixture of chemicals), non-resilient changes were observed suggesting that continuous/repeated irrigation with wastewater could lead to the accumulation of contaminants in soil and induce changes in bacterial communities with unknown functional consequences.