With growing myopia prevalence worldwide, effective strategies to prevent early-onset myopia are needed.To evaluate the efficacy of diversified segmental defocus optimization (DSDO) spectacle lenses with or without 0.01% atropine for myopia prevention.This was 1-year randomized placebo-controlled double-masked clinical trial conducted in the Department of Ophthalmology at Peking University People's Hospital from November 2023 to December 2024. Children aged 5 to 12 years with spherical equivalent refraction (SER) of 0.00 to 1.00 diopters (D) after cycloplegia were included, excluding those with ocular diseases, systemic diseases, or previous use of optical or pharmaceutical myopia control methods.Participants were randomly assigned in a 1:1:1 ratio to receive DSDO spectacles with placebo eye drops (DSDO group), DSDO spectacles with 0.01% atropine eye drops (DSDOA group), or single-vision spectacles with placebo eye drops (control group).The primary outcomes were the cumulative incidence rate of myopia (defined as SER ≤-0.50 D) and the percentage of participants with fast myopic shift (defined as a spherical equivalent myopic shift ≥0.50 D) over 1 year. Secondary outcomes included changes in SER, axial length, and subfoveal choroidal thickness.Of the 450 children initially randomized (DSDO group: mean [SD] age, 7.05 [0.12] years; 77 [51.3%] male; DSDOA group: mean [SD] age, 7.02 [0.14] years; 73 [48.7%] male; control group: mean [SD] age, 7.01 [0.11] years; 78 [52.0%] male), 370 (82.2%) completed the study, including 121 in the DSDO group, 125 in the DSDOA group, and 124 in the control group. The 1-year cumulative incidence rates of myopia in the DSDO, DSDOA, and control groups were 5.8% (7/121), 4.8% (6/125), and 15.3% (19/124), respectively, and the percentages of participants with fast myopic shift after 1 year were 15.7% (19/121), 9.6% (12/125), and 42.7% (53/124). Both DSDO and DSDOA groups showed significantly lower 1-year cumulative myopia incidence (DSDO: difference, 9.5%; 95% CI, 1.9-17.5; P = .02; DSDOA: difference, 10.5%; 95% CI, 3.3-18.4; P = .006) and the percentage of patients with fast myopic shift (DSDO: difference, 27.0%; 95% CI, 16.1-37.3; P < .001; DSDOA: difference, 33.1%; 95% CI, 23.1-42.8; P < .001) vs control. No significant differences were observed between DSDO and DSDOA groups.These data suggest that daily use of DSDO spectacles delays the onset of myopia among children without myopia, supporting DSDO spectacles without atropine as an alternative preventive method for children without myopia if supported with longer follow-up and replication by others.Chinese Clinical Trial Registry: ChiCTR2300077307.