This study aimed to compare the skeletal and dentoalveolar effects produced by slow maxillary expansion (SME) with the Leaf expander versus the conventional rapid maxillary expansion (RME) on digital dental casts, lateral and postero-anterior cephalometric radiographs. This is a superiority, two-center, two arms parallel balanced randomization trial. Patients in the mixed dentition were included with a transverse interarch discrepancy of at least 3 mm. An expansion screw using moderate continuous forces (Leaf group) was compared to a conventional RME screw (RME group). The primary response variable was the difference in maxillary intermolar width (U6-U6) measured at baseline (T0) and one-year follow-up (T1) on the digital dental casts. Other dento-skeletal variables were also measured on digital dental casts and cephalograms. Computer-generated block randomization was used with allocation concealed in sequentially numbered opaque sealed envelopes. The examiner was blinded on the type of expander used. Linear models were used for statistical analysis. Twenty-eight patients in the Leaf group and 28 patients in the RME group were randomized and included in the study. There were no dropouts. U6-U6 did not show a statistically significant difference between the two groups (-0.4 mm in favor of the RME group, 95% CI from -1.2 to 0.5, P = 0.365). As for the other secondary variables no statistically significant differences were found between the two groups except maxillary intercanine width (U3-U3, -0.9 mm in favor of the RME group, 95%CI from -1.5 to -0.3, P = 0.005) and maxillary skeletal width (Mx-Mx, -1.4 mm in favor of the RME group, 95%CI from -2.4 to -0.3, P = 0.013). No significant differences between the RME and Leaf groups were detected for any of the analyzed dento-skeletal variables except the T1-T0 differences in U3-U3 and Mx-Mx that were significantly greater in the RME group. The study was registered in the ISRCTN register on 08/11/2016 with the number ISRCTN18263886. No funding or conflict of interest to be declared.