Abstract We report on three trials of a MUC1 peptide vaccine for cancer prevention. Two trials were pilot studies evaluating vaccine immunogenicity and safety. One was in subjects with advanced colon adenomas, and the other in smokers at risk for lung cancer. The third trial was a multi-center, randomized placebo-controlled trial in subjects with advanced adenoma that included an assessment of the clinical efficacy of the vaccine to prevent recurrent adenoma. All trials successfully recruited their full complement of participants and the vaccine was well tolerated with no safety concerns. The response rate in the colon adenoma trials was 43% in the pilot study and 25% in the placebo- controlled multicenter trial. Only 10% of smokers responded to the vaccine. Higher levels of circulating myeloid derived suppressor cells (MDSC) were consistently associated with the lack of an immune response. This suggests that even in pre-malignancy immunosuppressive tendencies can impair vaccine immunogenicity. Responders to the vaccine demonstrated immune memory at one year. In the multicenter adenoma trial that evaluated the efficacy of the vaccine on adenoma recurrence, immune responders demonstrated an association with a reduced rate of adenoma recurrence. In future studies, patient selection based on circulating MDSC levels, or concomitant use of agents to counter MDSC immunosuppressive function or otherwise improve T cell function, should be considered. Citation Format: Robert E. Schoen. Lessons learned from clinical trials of MUC1 peptide vaccines for cancer prevention [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr IA016.