PURPOSE: To evaluate two different spectral-domain optical coherence tomography (SD-OCT) scan patterns in eyes with intermediate age-related macular degeneration (AMD) for the longitudinal assessment of drusen volume. METHODS: The data of 38 eyes of 38 AMD patients (age 69.97 $±$ 6.08 years) were included. The longitudinal drusen volume over 4 years was analyzed by annual SD-OCT raster scanning (field size 20 $times$ 15°). Two raster scan patterns (A/B) differed in the distance between neighboring B-scans (240 vs. 30 µm) and in the number of averaged frames (4 vs. 15). RESULTS: The mean drusen volume at baseline was 0.213 $±$ 0.100 mm3 (pattern A) and 0.219 $±$ 0.103 mm3 (pattern B) (p = 0.937). Linear mixed-effect models showed no significant difference for the change within 4 years for both pattern A (p = 0.8) and pattern B (p = 0.8). CONCLUSIONS: The results indicate that the performance of interpolation algorithms may be sufficient to balance for less dense raster scanning with regard to quantification of longitudinal drusen volume, which can be used as a surrogate marker for AMD progression in future clinical trials.