This study evaluated risk factors for increases in nuclear opacification of the lens in the Longitudinal Study of Cataract (1989-1993; Boston, Massachusetts), which included 764 participants. Baseline data on demographic, medical, and other risk factors were available from an earlier case-control study; follow-up visits were completed yearly over a 4-year period. The lens photographs taken at baseline and at each follow-up visit were graded using the Lens Opacities Classification System III protocol. Analyses evaluated which risk factors collected at baseline were related to increased nuclear opacification at follow-up. The MULCOX2 method, an extension of Cox regression for nested event-time data, was used to estimate the effects of the risk factors. This method accounted for the correlation between fellow eyes. Results showed that the risk of nuclear opacification increased with each year of age (relative risk (RR) = 1.07), white race (RR = 2.94), lower education (RR = 1.50), use of gout medications (RR = 2.32), current smoking (RR = 1.58), family history of cataract (RR = 1.39), and preexisting posterior subcapsular opacities (RR = 6.67). An association with early use of eyeglasses was also suggested (RR = 1.37). In conclusion, nuclear opacification was related to demographic and other variables, including potentially modifiable factors such as current smoking and use of gout medications. Most risk factors identified by this longitudinal study confirm those found by the original case-control study. The increased risk of nuclear opacities in whites appears to be a new finding.