Multimodal retinal imaging enables the detection of subretinal drusenoid deposits (SDD) with significantly greater accuracy compared to fundus photography. The study aimed to analyze a relationship between the presence of SDD, the clinical picture of AMD, and disease progression in a 3 year follow-up. A total of 602 eyes of 339 patients with a diagnosis of AMD, of which 121 (55%) had SDD confirmed in multimodal retinal imaging, were enrolled in the study. SDD was related to a more advanced stage of AMD (p = 0.008), especially with the presence of geographic atrophy (OR = 4.11, 95% CI 2.02–8.38, p < 0.001). Eyes with SDD presented significantly lower choroidal and retinal thickness (ATC: 210.5 μm, CRT: 277 μm, respectively) and volume (AVC: 0.17 mm3, CRV: 8.29 mm3, p < 0.001, respectively) compared to SDD-negative eyes (ATC: 203 μm, CRT: 277 μm; AVC: 7.08 mm3, 8.54 mm3, p < 0.001). Accordingly, the prevalence of pachychoroids and pachyvessels was significantly lower in the SDD present group than in eyes without SDD (p = 0.004; p = 0.04, respectively). Neither demographic factors, lipid profile, genetic predisposition, systemic vascular disease comorbidities, nor parameters of retinal vessels were affected by the presence of SDD. We found no effect of SDD presence on AMD progression (p = 0.12). The presence of SDD appeared to be related to local rather than systemic factors.