OBJECTIVE To determine the diagnostic accuracy in a real-world primary care setting of a deep learning–enhanced device for automated detection of diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS Retinal images of people with type 2 diabetes visiting a primary care screening program were graded by a hybrid deep learning–enhanced device (IDx-DR-EU-2.1; IDx, Amsterdam, the Netherlands), and its classification of retinopathy (vision-threatening [vt]DR, more than mild [mtm]DR, and mild or more [mom]DR) was compared with a reference standard. This reference standard consisted of grading according to the International Clinical Classification of DR by the Rotterdam Study reading center. We determined the diagnostic accuracy of the hybrid deep learning–enhanced device (IDx-DR-EU-2.1) against the reference standard. RESULTS A total of 1,616 people with type 2 diabetes were imaged. The hybrid deep learning–enhanced device’s sensitivity/specificity against the reference standard was, respectively, for vtDR 100% (95% CI 77.1–100)/97.8% (95% CI 96.8–98.5) and for mtmDR 79.4% (95% CI 66.5–87.9)/93.8% (95% CI 92.1–94.9). CONCLUSIONS The hybrid deep learning–enhanced device had high diagnostic accuracy for the detection of both vtDR (although the number of vtDR cases was low) and mtmDR in a primary care setting against an independent reading center. This allows its’ safe use in a primary care setting.