This paper reviews the evidence for how the What Works for Women and Girls: Evidence for HIV/AIDS Interventions (hereafter What Works) knowledge translation platform has made a difference in the global AIDS response. With an aim to increase use of evidence in policies and programmes to reach women and girls, the paper asks: What difference has What Works made? Has evidence from it informed the policies and programmes of donors? Has it informed national policies and plans? Has it contributed to the information used by civil society organisations (CSOs)? Has access to the What Works website been sufficient, or were other activities needed to enhance the use of the evidence from the website? This paper documents how the key components of the platform resulted in demonstrable change in HIV programming for women and girls, with the hope that lessons learned from this effort may assist others who are working to create cultures of evidence.