In preparation for trials of new HIV prevention methods; willingness to participate (WTP) was assessed in Beira; Mozambique. A totla of 1 019 women participating in an HIV incidence study; and 97 men participating in a separate WTP survey; were interviewed. When comparing the answers to questions that were identical in the two studies; WTP was higher among women than men for all prevention methods. Among women; WTP was highest for trials evaluating daily oral pre-exposure prophylaxis (PrEP; 84.4 reporting very likely to participate); followed by vaccination (77.8); daily vaginal gel use (67.7); coital vaginal gel use (67.1) and monthly vaginal ring use (47.7). Among men; WTP was highest for trials evaluating vaccination (57.6); followed by daily vaginal gel use for female sexual partners (52.5); daily oral PrEP (49.5); coital vaginal gel use for female sexual partners (46.4) and monthly vaginal ring use for female sexual partners (39.4). Among men; the most important motivators for trial participation were social benefits; whereas personal risks (most notably receiving injections and/or blood draws) were deterrents; this was not assessed in women. Other important lessons learnt are that male circumcision and antiretroviral drugs were not generally recognised as ways to prevent HIV; that having to use hormonal contraception during trial participation will likely reduce WTP; and that evening clinics are not likely to be popular. The barriers reported in this and other studies may be challenging but are not impossible to overcome