Purpose: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. Design: Multicenter, randomized, sham-controlled trial. Participants: Two-hundred ninety-two patients with bilateral large drusen. Methods: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. Main Outcome Measures: The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non–study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non–study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. Results: Progression to late AMD in the non–study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40–1.71; P = 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P = 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non–study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (–0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non–study eye (–0.48 and –0.56 letters/year, respectively; P = 0.628). Conclusions: Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.