ABSTRACT: BACKGROUND: It is known that being on antiretroviral therapy reduces the risk of HIV transmission through sex. However it remains unknown what the absolute level of risk of transmission is in a person on ART with most recent measured HIV plasma viral load < 50 c/mL in the absence of condom use. There are no data on risk of transmission for anal sex in MSM when the index partner is on ART. Methods/design The PARTNER study is an international, observational multi-centre study, taking place from 2010 to 2014 in which HIV serodifferent partnerships who at enrolment reported recently having had condom-less vaginal or anal sexual intercourse are followed over time, with 4-6 monthly reporting of transmission risk behaviour through a confidential self completed risk behaviour questionnaire and with 4-6 monthly HIV testing for the HIV negative partner. The objective is to study (i) the risk of HIV transmission to partners, in particular in partnerships that continue not to use condoms consistently and the HIV-positive partner is on therapy with a viral load < 50 copies/mL and (ii) why some partnerships do not use condoms, to describe the proportion who begin to adopt consistent condom use, and factors associated with this. For any negative partner who becomes infected phylogenetic analysis will be used following anonymisation of the samples to assess if transmission had been from the HIV infected partner. DISCUSSION: This observational study will provide missing information on the absolute risk of HIV transmission for both vaginal and anal sex when the index case is on ART with a VL < 50 copies/mL in the absence of condom use.