Adolescent girls and young women (AGYW) have a disproportionately high incidence of HIV compared to males of the same age in Uganda. AGYW are a priority sub-group for daily oral Pre-Exposure Prophylaxis (PrEP), but their adherence has consistently remained low. Short Message Service (SMS) reminders could improve adherence to PrEP in AGYW. However, there is paucity of literature about acceptability of SMS reminders among AGYW using PrEP. We assessed the level of acceptability of SMS reminders as a PrEP adherence support tool and the associated factors, among AGYW in Mukono district, Central Uganda. We consecutively enrolled AGYW using PrEP in Mukono district in a cross sectional study. A structured pre-tested questionnaire was administered to participants by three trained research assistants. Data were analyzed in STATA 17.0; continuous variables were summarized using median and interquartile range (IQR) while categorical variables were summarized using frequencies and percentages. Acceptability of SMS was defined as willingness to accept SMS reminders to support PrEP adherence and was assessed using the seven constructs of the theoretical framework of acceptability. The relationship between the outcome and independent variables was assessed using a modified Poisson regression with robust standard errors. During the month of August 2022, 142 AGYW with median age 22 years (IQR; 18, 24) of whom 80.3% owned a personal mobile phone were assessed. SMS reminders were highly acceptable [90.9%, 95% Confidence Interval (CI) [84.9, 95.0]]. Rural residence was negatively associated with acceptability of SMS reminders (aPR: 0.92, 95% CI (0.84, 0.99)) and having belief that SMS cannot breach individual’s privacy (aPR: 1.40, 95% CI (1.07, 1.84)) was positively associated with acceptability of SMS reminders. The acceptability of SMS reminders was high in this sub-population. SMS reminder can be leveraged to support AGYW to adhere to PrEP but should be designed in a way that maintains confidentiality, and supports AGYW living in rural settings.