Purpose: To evaluate the clinical and radiographic results of simultaneous implant placement using transcrestal sinus floor elevation (TSFE) with and without enamel matrix derivative (EMD) application. Materials and Methods: Twenty-four patients were randomly assigned into two groups: The EMD+TSFE group (n = 13 patients, 20 implants) received TSFE with EMD application, and the TSFE group (n = 11 patients, 20 implants) received TSFE without EMD application. The patients were recalled at 3 (T3) and 12 (T12) months postsurgery. The residual bone height (RBH), implant protrusion length (IPL), peri-implant sinus bone level (SBL), endo-sinus bone gain (ESBG), and implant stability (ISQ) were measured. Multivariate regressions were performed for the groups. Results: At T3, the ESBG was 3.72 ± 0.85 mm in the EMD+TSFE group and 3.10 ± 0.05 mm in the TSFE group, and there were statistically significant differences (P < .05). However, there were no statistically significant differences in ESBG at T12 between the groups (P > .05). ISQ values did not show a statistical difference between the groups at T1 and T3, but at T3 in the TSFE+EMD group, there was a statistical increase in the intragroup evaluation compared to the TSFE group. Conclusions: The use of EMD in TSFE procedures is effective in new bone formation at the apical part of the implant during the early healing period, but in the long term, no significant difference was shown between cases in which EMD was or was not used in terms of new bone formation and primary and secondary stabilization.