We conducted a mixed-method longitudinal evaluation of an HIV primary care practice transformation project in Washington, D.C. The project aimed to enhance organizational capacity to deliver culturally appropriate and patient-centered care for Latinxs living with HIV. Quantitative and qualitative data were simultaneously collected to capture the complex interactions among care providers, staff, and patients as well as to monitor practice changes that occurred as a result of the project implementation. The practice transformation intervention consisted of core competency workforce training, workflow redesign, and data-driven quality improvement strategies utilized to guide the intervention and to gather data from providers and patients. The mixed-methods approach facilitated meaningful change within the clinic that resulted in improved patient outcomes, patient experiences of care, and increases in staff’s perceived level of knowledge of patient-centered care and improved efficiencies in HIV health care service delivery.