BACKGROUND: Electronic health record (EHR)-linked clinical decision support (CDS) may impact primary care clinicians' (PCCs') clinical care opinions. As part of a clinic cluster-randomized control trial (RCT) testing a cancer prevention and screening CDS system with patient and PCC printouts (with or without shared decision-making tools [SDMT]) for patients due for breast, cervical, colorectal, and lung cancer screening and/or human papillomavirus (HPV) vaccination compared to usual care (UC), we surveyed PCCs at study clinics pre- and post-CDS implementation. Our primary aim was to learn if PCCs' opinions changed over time within study arms. Secondary aims including examining whether PCCs' opinions in study arms differed both pre- and post-implementation, and gauging PCCs' opinions on the CDS in the two intervention arms. METHODS: This study was conducted within a healthcare system serving an upper Midwestern population. We administered pre-implementation (11/2/2017-1/24/2018) and post-implementation (2/2/2020-4/9/2020) cross-sectional electronic surveys to PCCs practicing within a RCT arm: UC; CDS; or CDS + SDMT. Bivariate analyses compared responses between study arms at both time periods and longitudinally within study arms. RESULTS: Pre-implementation (53%, n = 166) and post-implementation (57%, n = 172) response rates were similar. No significant differences in PCC responses were seen between study arms on cancer prevention and screening questions pre-implementation, with few significant differences found between study arms post-implementation. However, significantly fewer intervention arm clinic PCCs reported being very comfortable with discussing breast cancer screening options with patients compared to UC post-implementation, as well as compared to the same intervention arms pre-implementation. Other significant differences were noted within arms longitudinally. For intervention arms, these differences related to CDS areas like EHR alerts, risk calculators, and ordering screening. Most intervention arm PCCs noted the CDS provided overdue screening alerts to which they were unaware. Few PCCs reported using the CDS, but most would recommend it to colleagues, expressed high CDS satisfaction rates, and thought patients liked the CDS's information and utility. CONCLUSIONS: While appreciated by PCCs with high satisfaction rates, the CDS may lower PCCs' confidence regarding discussing patients' breast cancer screening options and may be used irregularly. Future research will evaluate the impact of the CDS on cancer prevention and screening rates. TRIAL REGISTRATION: clinicaltrials.gov , NCT02986230, December 6, 2016.