Background: While a leading cause of morbidity and mortality in cancer, prior studies report low awareness of cancer-associated thrombosis (CAT) among adults with cancer. Despite multiple guideline endorsed thromboprophylaxis (TP) agents and evolving data for personalised TP strategies, objective willingness to engage and preferences for care within ambulatory settings, have yet been elucidated. Methods: Individuals commencing systemic anticancer therapies lung and gastrointestinal cancers enrolled in the TARGET-TP trial of risk-directed ambulatory TP (ANZCTRN12618000811202) reported awareness, preferences, and engagement (related to CAT and TP) at enrolment, using a 6-item study specific survey. Participants were informed regarding the impact of CAT and the rationale for the study as part of the consent process however surveys were completed prior to clot risk-assessment, before being allocated and informed of trial arm (observation or intervention), and with instruction to answer based on knowledge and beliefs before participating in the consent process. Experiences with TP were assessed longitudinally in trial participants randomised to enoxaparin, using the validated 15-item Anti-Clot Treatment Scale (ACTS). Results were reported descriptively, compared over time and among subgroups of interest - including cancer type, new vs previously treated, age, sex, stage and treatment centre (specialist/general). Results: Data from 273/328 (83%) trial participants who completed surveys were evaluated. One third (34%) reported being unaware of CAT, but, given information, nearly all (99%) were willing to be proactive to prevent clots, including use of anticoagulants (97%): oral (92%) vs injectable (82%). Individuals reported willingness to use injectable (vs oral) in hypothetical situations where the injectable agent offered greater efficacy (91%), reduced bleeding risk (86%), or was less likely to interact with cancer medicines (87%). Results were similar among subgroups except individuals with lung cancer who reported higher CAT awareness if receiving care at specialist vs general hospital (79% vs 56%, P = 0.02). Among 83/100 (83%) trial participants randomised to enoxaparin TP who completed at least one ACTS survey, burdens of TP were infrequently reported: high burden (4%), any burden (19%). The most burdensome aspect was inconvenience of daily treatment, and least burdensome aspect related to perceived bleeding risks. More than 86% of individuals reported benefits of TP. Perceived burdens/benefits were consistent over the 6-month reporting period and within subgroups. Conclusions: Findings demonstrate gaps in supportive cancer care education across health services that if overcome present an opportunity to harness an overwhelming willingness of individuals with cancer to proactively engage in clot prevention strategies. Clinical trial information: ANZCTRN12618000811202.