Nausea, vomiting and diarrhea are frequent co-occurring symptoms that can mask or mimic commonly occurring conditions, or rarely, more serious concerns. The Ending the HIV Epidemic's focus on increased widespread use of PrEP, a biomedical HIV prevention strategy, highlights the importance of discussing common clinical management scenarios. The use of oral PrEP formulations has demonstrated a "startup syndrome" which involves GI upset. This case challenge of a 32year old client admitted to the ED with GI symptoms highlights key PrEP considerations including a sexual health history. Clinicians should understand common complaints associated with oral PrEP start to improve differential diagnosis and appropriate intervention.