This study investigated the vulnerability to human immunodeficiency virus (HIV) infection and associated factors among married women in northwest Ethiopia.Methods: A community-based cross-sectional survey (n=657) was conducted from April 1 to 15,2020, in Metema District, northwest Ethiopia, in four randomly selected kebele administrations (thelowest level of local government). The inclusion criteria were married women aged ≥18 years residing with their husbands. Logistic regression analysis was conducted to identify factors associatedwith married women’s vulnerability to HIV infection.Results: Participants were on average 33.70±9.50 years and nearly one-fourth (n=148, 22.5%) wereidentified as vulnerable to HIV infection (i.e., experienced sexually transmitted disease symptoms oran extramarital affair of either spouse within the past 12 months). Only 18.9% reported sexual communication with their husband. Respondents who did not discuss the risk of HIV infection withtheir husbands had fivefold odds of vulnerability (adjusted odds ratio [AOR], 5.02; 95% confidenceinterval [CI], 1.43–17.5). Those who did not have premarital sex (AOR, 0.20; 95% CI, 0.05–0.77)had no worries about HIV infection (AOR, 0.27; 95% CI, 0.08–0.94), sufficient income (AOR,0.56; 95% CI, 0.16–0.86), and less than four children (AOR, 0.69; 95% CI, 0.50–0.97) had decreased odds of being vulnerable to HIV than their counterparts.Conclusion: Not discussing risk of HIV infection with husband was a major factor of vulnerabilityto HIV infection as was premarital sex, worry about HIV, income, and number of children. Measuresto strengthen couple’s sexual communication and support economical stability is important for decreasing HIV vulnerability