BACKGROUND/AIMS: The effectiveness of occlusion therapy for the treatment of amblyopia is a research priority. The authors describe the design of the Monitored Occlusion Treatment for Amblyopia Study (MOTAS) and its methodology. MOTAS will determine the dose-response relation for occlusion therapy as a function of age and category of amblyopia. METHODS: Subjects progress through up to three study phases: (1) Assessment and baseline phase: On confirmation of eligibility, and after parental consent, baseline visual functions are determined, and spectacles prescribed as necessary; (2) Refractive adaptation phase: Subjects wear spectacles full time and return to clinic at 6 weekly intervals until 18 weeks, by which time all improvement due to refractive correction is complete; (3) Occlusion phase: All subjects are prescribed 6 hours of occlusion per day. Daily occlusion is objectively monitored using an occlusion dose monitor (ODM). Outcome variables: visual acuity (logMAR charts), log contrast sensitivity (Pelli-Robson chart), and stereoacuity (Frisby) are assessed at 2 weekly intervals until gains in visual acuity cease to be statistically verifiable. CONCLUSION: Four methodological issues have been addressed; firstly, baseline stability of visual function; secondly, differentiation of refractive adaptation from occlusion; thirdly, objective measurement of occlusion dose and concordance; fourthly, use of validated outcome measures.