To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD).Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth.In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively).Individuals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non-significant, associations.