The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundaci on Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consor- tium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad [MINECO] through the Instituto de Salud Carlos III [ISCIII] and Red Temática de Investigaci on del Cáncer [RTICC] del ISCIII [RD12/0036/0036]), by the Junta de Castilla y Le on (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Regi on de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723, 2014SGR850, 2017SGR1085, 2021SGR01354 by the Fundaci on Caja de Ahorros de Asturias and by the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. Anna Palomar-Cros is supported by a MINECO (Spanish Ministry of Econ- omy) fellowship (PRE2019-089038). Camille Lassale is supported by a Ramon y Cajal Fellowship RYC2020-029599 funded by MCIN (Spanish Ministry of Science and Innovation) and EI FSE “Invest in your future”., Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (, AGAUR 2014SGR850, 2017SGR1085, 2017SGR723, 2021SGR01354, Catalan Government‐Agency for Management of University and Research Grants, Centro de Excelencia Severo Ochoa 2019‐2023, Consejería de Salud of the Junta de Andalucía PI‐0306‐2011, Consejería de Sanidad de la Región de Murcia, Regional Government of the Basque Country, Conselleria de Sanitat of the Generalitat Valenciana 2010ACUP 00310, AP_061/10, EI FSE, European Commission grants FOOD-CT- 2006-036224-HIWATE, Fundación Caja de Ahorros de Asturias, Fundación Marqués de Valdecilla API 10/09, Generalitat de Catalunya, ICGC International Cancer Genome Consortium CLL, Instituto de Salud Carlos III‐FEDER PI08/0533, PI08/1359, PI08/1770, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034, PS09/00773, PS09/01286, PS09/01662, PS09/02078, Junta de Castilla y León LE22A10‐2, MCIN, MINECO, RTICC RD12/0036/0036, Red Temática de Investigación del Cáncer, Spanish Association Against Cancer (AECC) Scientific Foundation, Spanish Ministry of Economy PRE2019‐089038, Spanish Ministry of Science and Innovation, University of Oviedo