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Available freshwater scarcity significantly affects sustainable food production for the rapidly growing population. This problem has forced people in most parts of the world to use wastewater as a viable solution. However, wastewater reuse has some deleterious effects on human and environmental health. This study was designed to investigate the health risks (HRs) of heavy metals (HMs) from vegetables irrigated with untreated and treated wastewater. The composite wastewater was collected at various sites in Arba Minch town and subjected to aerobic-anoxic treatment. Treated and untreated wastewater (UTW) was used to irrigate vegetables (lettuce, cabbage and tomato), and HM results were compared with the control (tap water) and standards. Water, soil and vegetables were investigated for various physical and chemical properties. Human health effects due to vegetable consumption were analyzed using HR- index (HRI), target hazard quotient (THQ) and hazard index (HI). The results revealed that most of the water quality indexes were significantly enhanced after aerobic-anoxic treatment, suggesting that wastewater collected from different sites was suitable for biodegradation. Soil physicochemical analyses also showed that pH, cation exchange capacity, organic carbon and organic matter were higher for UTW irrigated soil. Heavy metal concentrations were relatively greater in soils than water used for irrigation purposes and vegetables. The HM concentration in vegetables was higher for UTW than for treated and tap water irrigated vegetables. In vegetables, the order of HM content was Fe > Mn > Zn > Pb > Cu > Cd. Tomato followed by cabbage and lettuce accumulated significant amount of HMs (Fe > Mn > Zn > Pb > Cu > Cd) in their different organs (fruit/leaf>root>stem). The individual and combined health indexes (HRI, THQ and HI) showed that Pb and Cd have values greater than unity for wastewater irrigated vegetables, which could result in non-carcinogenic disease for short/lifetime exposure in adults and children. Overall, consumption of vegetables can be safer when grown with treated effluent than with UTW., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)