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This study aimed to examine the effectiveness of Human Immunodeficiency Virus (HIV)-assisted smartphone applications in the treatment of HIV/AIDS patients in Vietnam. A cross-sectional study was performed in two urban outpatient clinics in Hanoi from May to December 2019. A simple random sampling method and a structured questionnaire were used to recruit 495 eligible participants and to collect data. Multivariable modified Poisson regression and multivariable linear regression models were employed to investigate the factors associated with the willingness to pay (WTP) and amount of money patients were willing to pay. Approximately 82.8% of respondents were willing to pay for the hypothetical applications, with the mean amount the participants were willing to pay of Vietnam Dong (VND) 72,100/month. Marital status (separate/divorced/widow: Odds ratio (OR) = 1.28, 95% confidence interval (CI) = (1.09; 1.50) and having spouse/partner: OR = 1.18, 95% CI = (1.03; 1.36)) and using health services (OR = 1.03, 95% CI = (1.01; 1.04)) were positively associated with nominating they would be WTP for the app, whereas the duration of antiretroviral treatment (ART) (OR = 0.98, 95% CI = (0.96; 0.99)) had a negative association. The frequency of using health services (β = 0.04, 95% CI = (-0.07; -0.01)) was negatively associated with the amount of WTP. High levels of WTP revealed the feasibility of implementing smartphone-based apps for HIV treatment. This study implied the necessity to consider a co-payment system to reach populations who were in need but where such applications may be unaffordable in lieu of other treatment-associated expenses. Developers also need to pay attention to privacy features to attract single people living with HIV/AIDS and additional measures to initiate people with a long duration on ART into using the applications.