We evaluated subthreshold photocoagulation using endpoint management (EPM) for the treatment of diabetic macular edema (DME). The study enrolled 10 eyes from 10 patients (6 men and 4 women) with DME. The entry criteria included central macular thickness (CMT) ≥ 300 μm and decimal visual acuity (VA) ≤ 0.5. The primary endpoints were VA (logMAR) and CMT at 6 months follow-up. Secondary endpoints included fundus autofluorescence, macular volume (MV), and macular sensitivity (MS). We used the PASCAL Streamline Yellow® (wavelength, 577 nm) system to perform grid pattern laser photocoagulation at 50% of the threshold (size, 100 μm; duration, 0.015 s; spacing, 0.5; and energy, 4.5-7.8 mJ). At 6 months posttreatment, CMT was significantly decreased, while there were no significant changes in macular sensitivity, mean BCVA (logMAR), or macular volume. Autofluorescence imaging revealed no changes after treatment in 6 of 10 eyes. No eyes exhibited subjective symptoms of scotoma after photocoagulation. Optical coherence tomography showed the complete resolution of macular edema in 4 eyes (40%) after a single treatment; MS was increased in all 4 of these eyes at 6 months posttreatment. In conclusion, subthreshold photocoagulation using EPM is safe and effective for DME treatment and preserves MS. This trial is registered with UMIN000012401.