To evaluate the choriocapillaris flow in regions of enlarged or new incident drusen in patients with early and intermediate age-related macular degeneration (AMD). We retrospectively reviewed and analyzed structural optical coherence tomography (OCT) and OCT angiography (OCTA) images of consecutive patients with early or intermediate AMD evaluated at the Doheny-UCLA Eye Centers between 2015 and 2018. All patients were imaged using a Cirrus OCT, and only one eye was included in the study. To be eligible for this analysis, patients were required to have a 3 × 3-mm OCTA scan acquired during the first visit (considered as baseline) and a fovea-centered 512 × 128 macular cube (6 × 6 mm) acquired at both the baseline visit and after a minimum of 1 year follow-up. The drusen maps generated from the macular cubes were used to generate a drusen area (DA) measurement and compute the difference between baseline and follow-up (ΔDA). After registering the structural OCTs to the baseline choriocapillaris (CC) OCTA, we analyzed and compared the baseline flow deficits (FD) within drusen-free region (FDDF), regions into which drusen enlarged or expanded at follow-up (FDEN), and regions in which new incident drusen (FDND) appeared at follow-up. Forty-six patients were eligible for the analysis and had a mean follow-up of 1.47 years. Twelve eyes of 12 subjects had a ΔDA < 0.1 mm2. In these eyes, only the FDDF was calculated (40.37 ± 2.29%) and it was not significantly different from the FDDF of eyes with ΔDA ≥ 0.1 mm2 (40.25 ± 4.37%, p = 0.849). When comparing the different regions within the eyes with ΔDA ≥ 0.1 mm2, there was no significant difference between FDED and FDND (43.61 ± 4.36% and 44.16 ± 2.38%, p = 528), but both were significantly higher than FDDF (p = 0.001 and p < 0.001, respectively). Significant CC flow impairment is present under regions of intact retinal pigment epithelium (RPE) where existing drusen will enlarge into or new drusen will appear within 2 years. These findings suggest that location of drusen may not be stochastic but may be driven by regional deficits in the choriocapillaris.