Scarce evidence is available on the impact of real-world smoking cessation treatment on subsequent health outcomes, such as incidence of chronic disease. This study compared two cohorts of people that smoke-those that enrolled in a smoking cessation program, and a matched control that had not accessed the program-to assess the incidence of cancer, chronic obstructive pulmonary disease, diabetes, hypertension, and major cardiovascular events over a 5-year follow-up period. We selected five sub-cohorts with matched treatment-control pairs in which both individuals were at risk of the five chronic diseases. Incident chronic disease from index date until December 31, 2017, was determined through linkage with routinely collected healthcare data. The cumulative incidence of each chronic disease was estimated using the cumulative incidence function with death as a competing risk. Gray's test was used to test for a difference between matched treatment and control groups in the chronic disease-specific cumulative incidence function over follow-up. Analyses were stratified by sex. Among females, cumulative incidence of diabetes was higher over follow-up for the treatment group (5-year cumulative incidence 5.8% vs 4.2%, p = 0.004), but did not differ for the four other chronic diseases. Among males, cumulative incidence of chronic obstructive pulmonary disease (12.2% vs 9.1%, p < 0.001) and diabetes (6.7% vs 4.8%, p < 0.001) both had higher 5-year cumulative incidence for the treated versus control groups but did not differ for the other three chronic diseases. We conclude that accessing primary-care based smoking cessation treatment is associated with increased incidence of diabetes for both sexes, and chronic obstructive pulmonary disease for males (possibly due to under diagnosis prior to treatment), within 5 years of treatment. The associations detected require further research to understand causal relationships., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DB has received investigator-initiated grant support from Pfizer Canada, Ontario Ministry of Health and Long-Term Care, and the Canadian Institutes of Health Research (CIHR). CdO reports receiving grant funding from CIHR, University of Toronto, Medical Research Council, National Institutes of Health, Centre for Addiction and Mental Health (CAMH), Ontario Ministry of Health and Long-Term Care, Canadian Centre for Applied Research in Cancer Control and Ontario Mental Health Foundation. PS reports receiving funding from CCSRI, CIHR, Canadian Partnership Against Cancer, Centre for Addiction and Mental Health (CAMH), Health Canada, Medical Psychiatry Alliance, Ontario Ministry of Health and Long-Term Care, Ontario Neurotrauma Foundation and the Public Health Agency of Canada. PS also reports funding from the following commercial organizations: Patient-Centred Outcome Research Institute and Pfizer. PS has received honoraria in the past 3 years from University of Ottawa Heart Institute, Royal College of Physicians and Surgeons of Canada, Royal Victoria Regional Health Centre, Department of Family and Community Medicine at the University of Toronto, Northern Ontario School of Medicine, Canadian Partnership Against Cancer, Battle River Treaty 6 Healthcare, Lung Association of Nova Scotia, Exchange Summit, Toronto Public Health, Ontario Association of Public Health Dentistry and ECHO. PS has been retained as an expert witness by the Ontario and New Brunswick provincial governments in litigation against the tobacco industry. PS was a member and co-chaired the Ministry of Health’s Ontario Smoke Free Strategy cessation subcommittee. Through an open tender process, Johnson & Johnson, Novartis and Pfizer are vendors of record for providing free/discounted smoking cessation pharmacotherapy for research studies in which PS and LZ are principal or co-investigator. PK reports receiving grant funding from CIHR and the Ontario Ministry of Health and Long-Term Care. LR reports receiving grant funding from CIHR, SSHRC, New Frontiers in Research Fund, Canada Research Chairs and the Connaught Foundation. LZ reports receiving grant funding from Pfizer, Ontario Ministry of Health and Long-Term Care, Health Canada, CIHR and CCSRI. LZ also received honoraria and travel funds from Pfizer and University of Ottawa Heart Institute. RS reports receiving funding from CIHR, Terry Fox Research Institute, Garron Family Cancer Centre and Sick Kids Foundation, Canadian Society of Colon and Rectal Surgeons, Sunnybrook Foundation, Pediatric Oncology Group of Ontario, Ontario Institute for Cancer Research, PSI Foundation, C17 Research Network, Cancer Care Ontario, Canadian Centre for Applied Research in Cancer Control, Canadian Breast Cancer Foundation, Sunnybrook AFP Innovation Fund, CCSRI, Ministry of Health and Long-Term Care and the Ontario Medical Association. No other disclosures were reported. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Baliunas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)