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Background In this study, an alternative and complementary method to those approaches currently used to estimate alcohol consumption by the population is described. This method, known as wastewater-based epidemiology (WBE), allows back-calculating the alcohol consumption rate in a given population from the concentrations of a selected biomarker measured in wastewater. Methods Composite (24-h) wastewater samples were collected at the inlet of 17 wastewater treatment plants located in 13 Spanish cities for seven consecutive days in 2018. The sampled area covered 12.8% of the Spanish population. Wastewater samples were analyzed to determine the concentration of ethyl sulfate, the biomarker used to back-calculate alcohol consumption. Results Alcohol consumption ranged from 4.5 to 46 mL/day/inhabitant. Differences in consumption were statistically significant among the investigated cities and between weekdays and weekends. WBE-derived estimates of alcohol consumption were comparable to those reported by its corresponding region in the Spanish National Health Survey in most cases. At the national level, comparable results were obtained between the WBE-derived annual consumption rate (5.7 ± 1.2 L ethanol per capita (aged 15+)) and that reported by the National Health Survey (4.7 L ethanol per capita (aged 15+)). Conclusions This is the largest WBE study carried out to date in Spain to estimate alcohol consumption rates. It confirms that this approach is useful for establishing spatial and temporal patterns of alcohol consumption, which could contribute to the development of health care management plans and policies. Contrary to established methods, it allows obtaining information in a fast and relatively economical way., The authors would like to acknowledge all the city councils of the cities participating in this study for their collaboration as well as the operators of the WWTPs for their assistance in the collection of the wastewater samples, especially to: Cristian Mesa and Angela Vidal from Aigues de Barcelona (Barcelona WWTP), Jordi Palatsi from Aqualia (Lleida WWTP), Viaqua and Concello de Santiago de Compostela, the Public Entity of Wastewater Treatment (EPSAR) of the Generalitat Valenciana and especially to Fernando Llavador. Luis Aceiton, Enrique Albors, Angel Jiménez, Maria José Tarrega, Sonia Tristante and all the personal of the WWTPs (Aguas de Valencia, Spain), Sociedad de Fomento Agrícola Castellonense (FACSA, Castellón), and especially WWTP operators Santiago Querol and Sara Gargallo are acknowledged for providing wastewater samples from Castellón, as well as Subdirección General de Gestión del Agua, Ayuntamiento de Madrid, for allowing the collection of samples from Madrid.