This article builds upon Paul Preciado’s conceptualisation of pharmaco-pornographic power to understand the ongoing affects and effects of Pre-Exposure Prophylaxis (PrEP) on queer men’s sexual socialities and subjectivities. Drawing from a new-materialist epistemology, we analyze data from a sexual health pilot study in NYC to trace the techno-sexual health assemblages forming in queer life worlds. Our analysis suggests that these assemblages, entangling PrEP and other pharmacological substances, pornographic imaginaries together with mediatic technologies and public health rationalties, are creating paradoxical desires and practices of intimacy that are both normative and exceed rational health-actor logics and normative understandings of risk. These effects have population-level biopolitical implications.