The primary objective of this study was to characterize normal variation in radiographic joint space of the knee in a large sample of healthy young adults and to identify factors that contribute to this variation. We measured radiographic knee joint space in 279 skeletally mature subjects, age between 16 and 22 years, who participated in the Fels Longitudinal Study. Minimum joint space was measured in the medial and lateral knee compartments. Independent sample t tests and correlation analyses were performed to examine sex differences and associations between joint space, joint size, and body size [weight, stature, body mass index (BMI)]. Results show that young men have thicker articular cartilage than young women in both the medial and lateral compartments of the knee. Significant positive correlations were found between joint space and body size measures in the total sample. When the sexes were considered independently, however, correlations between joint space and body size were significant in men only. Regression analyses of the combined-sex sample identified sex, BMI, and joint width as significant explanatory factors of medial joint space, together accounting for 26% of the observed variance. In contrast, sex was the sole significant explanatory factor of lateral joint space, explaining 19% of the observed variance. Results of this study show that during early adulthood, when articular cartilage is healthy and at its peak thickness, men have thicker knee cartilage than women. At this young age body size accounts for a modest proportion of the variation observed in knee cartilage thickness.