Background: There is limited published data regarding safety and toxicity of Sars-CoV-2 vaccination in patients with cancer. This may contribute to vaccine hesitancy amongst some members of this vulnerable cohort (Nguyen 2022). Methods: SerOzNET (ACTRN12621001004853) is a large prospective cohort study of adults and children with cancer undergoing Sars-CoV-2 vaccination. Participants undertake surveys by text message link sent to their mobile phone, or on an iPad provided in clinic. A validated hesitancy survey is undertaken at enrolment (Oxford COVID-19 Vaccine Confidence and Complacency Scale), and prior to the 3^rd vaccine dose. For children, a parental survey is also collected. Quality of life is assessed with serial EORTC QLQ-C30 (adults) or PedsQL (children, self- and parent- report) at baseline and serially throughout the study. Patient- reported vaccine toxicity is assessed by patient-reported CTCAE items for common vaccine related AEs and patient-reported impact of vaccination on cancer treatment (delays, hospitalisations). Medically ascertained vaccine toxicity is assessed by study investigators one month after the 3^rd vaccination dose. Results: Five hundred and four participants have been enrolled (403 adults (80%) and 101 children (20%)). Hesitancy: At baseline, 351 adults (88%) and 56 children (55%) responded. The adult cohort was predominantly female (67.2%) with an average age of 53.8 years. Preliminary analysis showed similar levels of vaccination concerns between baseline (mean score = 18.4, SD = 5.1) and follow-up pre-3^rd dose (mean score = 17.9, SD = 5.7) in adults. We will present results regarding whether self-reported COVID-19 vaccine toxicity after the first dose was related to change in hesitancy scores at follow-up, which may have implications for COVID-19 vaccine booster willingness. Patient toxicity surveys have been returned post dose 1 for 445/497 (91%), post dose 2 for 417/457 (91%) and post dose 3 for 280/334 (84%). Incidence of any AEs was high (77-100% depending on age and dose), however the incidence of severe AEs (patient reported) was low (0-10% depending on age and dose). Interruptions to cancer treatment after vaccination were uncommon (2-12%). Pain at the injection site was the most commonly reported AE for all ages and doses. Hospital admissions (any reason) were reported post dose 1 in 4/15 children aged 5-12, but were uncommon in older adolescents and adults. The most common systemic adverse effect was rigors in children 5-12, while adolescents and adults reported fatigue most frequently. Quality of life analysis is ongoing and will be presented at the meeting. Conclusions: It is feasible to collect detailed toxicity and quality of life data in a large cohort of cancer patients receiving COVID-19 vaccinations. Data to date are reassuring that severe adverse events and interruptions to cancer therapy are uncommon. Clinical trial information: ACTRN12621001004853.