Abstract Objectives To provide a higher degree of evidence on the efficacy of Miniscrew-Assisted Rapid Palatal Expansion (MARPE) in late adolescents and adults, thereby applying the Dutch Maxillary Expansion Device (D-MED). Materials and methods D-MED was developed as an individualized, 3D-designed, and fabricated MARPE appliance supported by 4 palatal miniscrews. Patients from the age of 16 onwards with transverse maxillary deficiency were enrolled consecutively. Pre-expansion and immediate post-expansion CBCTs and intra-oral scans were acquired and measurements of skeletal, alveolar, and dental expansion as well as dental and periodontal side-effects were performed. Results Thirty-four patients were enrolled (8 men, 26 women) with mean age 27.0 ± 9.4 years. A success rate of 94.1% was achieved (32/34 patients). The mean expansion duration, or mean observation time, was 31.7 ± 8.0 days. The mean expansion at the maxillary first molars (M1) and first premolars (P1) was 6.56 ± 1.70 mm and 4.19 ± 1.29 mm, respectively. The expansion was 60.4 ± 20.1% skeletal, 8.1 ± 27.6% alveolar, and 31.6 ± 20.1% dental at M1 and 92.2 ± 14.5% skeletal, 0.0 ± 18.6% alveolar, and 7.8 ± 17.7% dental at P1, which was both statistically ( p < 0.001) and clinically significant. Buccal dental tipping (3.88 ± 3.92° M1; 2.29 ± 3.89° P1), clinical crown height increase (0.12 ± 0.31 mm M1; 0.04 ± 0.22 mm P1), and buccal bone thinning (− 0.31 ± 0.49 mm M1; − 0.01 ± 0.45 mm P1) were observed, while root resorption could not be evaluated. Conclusions MARPE by application of D-MED manifested its efficacy in a prospective clinical setting, delivering a high amount of skeletal expansion with limited side-effects in late adolescents and adults. Clinical relevance Higher quality evidence is supportive of MARPE as a safe and successful non-surgical treatment option for transverse maxillary deficiency.