On Earth, tissue weight generates compressive forces that press on body structures and act on the walls of vessels throughout the body. In microgravity, tissues no longer have weight, and tissue compressive forces are lost, suggesting that individuals who weigh more may show greater effects from microgravity exposure. One unique effect of long-duration microgravity exposure is spaceflight-associated neuroocular syndrome (SANS), which can present with globe flattening, choroidal folds, optic disk edema, and a hyperopic visual shift. To determine whether weight or other anthropometric measures are related to ocular changes in space, we analyzed data from 45 individual long-duration astronauts (mean age 47, 36 male, 9 female, mean mission duration 165 days) who had pre- and postflight measures of disk edema, choroidal folds, and manifest ocular refraction. The mean preflight weights of astronauts who developed new choroidal folds [78.6 kg with no new folds vs. 88.6 kg with new folds ( F = 6.2, P = 0.02)] and disk edema [79.1 kg with no edema vs. 95 kg with edema ( F = 9.6, P = 0.003)] were significantly greater than those who did not. Chest and waist circumferences were also significantly greater in those who developed folds or edema. The odds of developing disk edema or new choroidal folds were 55% in the highest- and 9% in the lowest-weight quartile. In this cohort, no women developed disk edema or choroidal folds, although women also weighed significantly less than men [62.9 vs. 85.2 kg ( F = 53.2, P < 0.0001)]. Preflight body weight and anthropometric factors may predict microgravity-induced ocular changes.