AbstractOral pre‐exposure prophylaxis (PrEP) effectiveness is directly correlated with medication adherence. Grady Health System (GHS) developed a PrEP program to optimize PrEP uptake in Atlanta, Georgia. The purpose of this study is to determine PrEP medication adherence and its associated factors during the first 18 months of the program's implementation. A single‐center, retrospective chart review was conducted on patients enrolled in a PrEP program in Atlanta, Georgia, between June 1, 2018 and February 29, 2020, who received more than one PrEP prescription. The primary outcome was mean adherence to PrEP, using the medication possession ratio (MPR). This study included 154 primarily young patients (mean 34 years of age), Black (70.8%), uninsured (59.1%), and cisgender men (62.3%). Mean PrEP adherence was 89.2%; 77.3% of patients had an MPR ≥ 80% (high adherence). Of all patients, 71 (46%) met PrEP discontinuation criteria. This PrEP program demonstrated high levels of PrEP adherence with discontinuation rates similar to other PrEP programs nationwide, despite a higher index of social vulnerability in the area. Future areas of research include identifying the specific program‐related factors that may optimize PrEP adherence in areas with high indices of social vulnerability.