Display omitted •Agro-industrial treated wastewater was reused for tomato and broccoli irrigation.•The main physico-chemical properties of wastewater met the Italian standards for irrigation reuse.•Quantity and quality of crops were not affected by wastewater.•No impact of wastewater on chemical properties of irrigated soil was observed.•Low level of fecal indicator was found in plants, tomato fruits and broccoli heads. In many countries of the Mediterranean region, characterized by frequent drought periods, agricultural production often occurs under water deficiency or conditions that cause the depletion of the existing water resources. In these areas, the reuse of reclaimed wastewater for crop irrigation could contribute to mitigate/decrease water shortage, support the agriculture sector and protect groundwater resources. In 1.5-year field experiments in Southern Italy (Apulia Region), the effects of irrigation with treated agro-industrial wastewater on soil properties, crops yield and qualitative traits of crop products, including their microbiological safety, were assessed. Groundwater (GW), secondary treated wastewater (SW) and tertiary treated wastewater (TW) from an innovative “on-demand” UV disinfection system were used to irrigate tomato and broccoli, cultivated in succession. The three irrigation water sources and the corresponding irrigated soils, plants and crop products were analyzed for the main physico-chemical characteristics, quali-quantitative parameters and fecal indicators. SW and TW showed higher values of the main physico-chemical parameters than GW. SW irrigated soil resulted in a significant increase of NH4-N, Na+, SAR, EC (below the threshold value beyond which a soil is defined as saline) during the first tomato crop cycle, and of pH during the broccoli growing season. Irrigation with treated wastewater did not significantly affect the marketable yield nor the qualitative traits of tomato and broccoli crops, except for the Na+ and NO3− content (below the threshold levels defined by the European guidelines for vegetables). High levels of E. coli (above the Italian limit for reuse), Fecal coliforms and Fecal enterococci (up to 104 CFU 100ml−1) were observed in the SW and, when chlorination was not done, in the TW. Nevertheless, E. coli was not isolated from any sample of soil, plant and crop product, probably due to its rapid die-off. Moreover, low concentrations of Fecal coliforms and Total heterotrophic count were found in plant and crop product. The drip irrigation system used, which avoided the close contact between water and plant, may have contributed to this. Under the conditions applied in this study, the reuse of treated agro-industrial wastewater for irrigation can be considered an effective way to cope with agricultural water shortage in the Mediterranean area.