Background: Anticipatory nausea (AN) and vomiting are unpleasant symptoms observed in anticipation of chemotherapy regimens. It is best described as a learned response through classical conditioning when one or more distinctive features of the chemotherapy clinic (conditioned stimuli) associated with the administration of emetogenic chemotherapy (unconditioned stimuli) trigger the emetogenic reflex. Little is known about AN's occurrence after the advent of the new neurokinin-1 antagonist. This prospective study evaluated AN's prevalence in ambulatory breast cancer patients receiving high effective antiemetic prophylaxis and evaluated potential predictors of AN. Methods: This prospective observational study was performed at a single Brazilian Institution. Key inclusion criteria were patients aged 18 years or older with breast cancer scheduled to receive anthracycline chemotherapy with an appropriate antiemetic regimen, including a neurokinin-1 receptor antagonist, a serotonin-3 receptor antagonist, and a corticosteroid. Eligible patients used a diary to record nausea, vomiting, and use of rescue medication in the first 2-cycle of treatment through 120 after infusion. AN was assessed before chemotherapy on day 1 of cycle two. We excluded patients with nausea and vomiting presented 24h before cycle one and patients who did not receive standard antiemetic prophylaxis. Results: Between August 04, 2020, and August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50,8 (28 – 69), the majority had stage III (53,8%) and received chemotherapy with curative intent (94%). During cycle 1, the frequency of overall nausea and vomiting was 67.31%, and severe nausea and vomiting (defined as grade > 4 at a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had AN (19.23%). The occurrence of nausea and vomiting during cycle one was the only statistically significant predictor of AN (OR = 16, 95% CI 2.4, 670.9, p-value = 0.0003). Conclusions: The prevalence of AN is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control on cycle one remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on cycle one to avoid AN. Clinical trial information: NCT04785495.