There a gradual transformation of the HIV epidemic with the emergence of antiretroviral therapy. Adherence to daily pill intake is vital for optimal HIV viral suppression. A strategic approach to enhancing adherence is the development of long-acting injectable ART (LAI-ART). Patients’ willingness to accept LAI-ART is a key determinant to the success of these novel therapies, but data is lacking in Africa and Ghana. This study assessed the willingness to accept LAI-ART among patients attending HIV clinic in Accra, Ghana. A cross-sectional study was conducted among 309 patients attending HIV clinic at the Infectious Disease Center of the Korle-Bu Teaching Hospital from July to October 2023. Data on perspectives on LAI-ART was collected using a structured questionnaire. Willingness was measured after exposure to a structured educational session to increase awareness or knowledge on LAI-ART. Descriptive statistics was used to summarize the demographic and clinical characteristics. Bivariate and multivariate analysis was performed with Fisher’s exact or Chi square test and logistic regression respectively. Most (71.5%) participants were female, above 50 years (46.3%) and were employed (70.6%). Majority were on a single-pill regimen (80.2%), adherent (86.7%), and had no prior awareness about LAI-ART (69.9%). After structured educational session, 89.6% showed a preference for LAI-ART, with a preferred frequency of injections every 6 months (67.3%). Almost 50% did not prefer self-administration of LAI- ART. Thirty-two percent had concerns about LAI-ART, and about 72% of PLHIV were willing to pay for LAI-ART. Participants’ willingness to accept LAI-ART reflected a hypothetical or informed preference and potential acceptability rather than observed behavior due to structured educational session. More education on LAI-ART is needed. LAI- ART presents an opportunity to increase access and adherence to HIV treatment. Further studies assessing potential barriers and how to address them will aid in the success of this treatment regimen.