This in vitro study evaluated the influence of combined coffee staining and simulated brushing-induced color changes and surface roughness on 3D-printed orthodontic retainers. Specimens measuring 10 × 10 × 0.75 mm3were obtained either by conventional vacuum forming or 3D printing at four print angulations (0°, 15°, 30°, and 45°) (n = 10). The prepared specimens were immersed in a coffee beverage and then mechanically brushed using a simulating device. The specimen’s color difference (ΔE) and surface roughness (Ra) were quantified using a spectrophotometer and a non-contact profilometer, respectively. The highest and lowest mean ΔE values were recorded for the 3D-printed-45° (4.68 ± 2.07) and conventional (2.18 ± 0.87) groups, respectively. The overall mean comparison of ΔE between the conventional and 3D-printed groups was statistically significant (p< 0.01). After simulated brushing, all groups showed a statistically significant increase in the Ra values (p< 0.01). The highest Ra was in the 3D-printed-45° (1.009 ± 0.13 µm) and conventional (0.743 ± 0.12 µm) groups, respectively. The overall ΔE of 3D-printed orthodontic retainers was not comparable to conventional VFRs. Among the different angulations used to print the retainers, 15° angulations were the most efficient in terms of color changes and surface roughness and were comparable to conventional VFRs.