Background: Despite widespread use of weight-and length-based anthropometric indexes as proxies for adiposity, little is known regarding the extent to which they correspond with fat mass (FM) or fat-free mass (FFM) during infancy. Objective: This study aimed to examine associations of 3 derived indicators-weight-for-age z score (WFAZ), weight-for-length score (WFLZ), and body mass index z score (BMIZ)-with FM, percentage of FM, and FFM measured by air-displacement plethysmography during the first 5 mo of life. Design: Applying prospectively collected data from 1027 infants in a Colorado prebirth cohort, we used multivariate regression to evaluate associations between the derived indicators and body composition at birth and at 5 mo, and with change (D) during follow-up. Results: At birth, all 3 derived indicators were more strongly associated with FFM than with FM. Each unit of WFAZ corresponded with 0.342 kg FFM (95% CI: 0.331, 0.351 kg FFM), compared with 0.121 kg FM (95% CI: 0.114, 0.128 kg FM) (P , 0.0001); similar trends were observed for WFLZ and BMIZ. By 5 mo, WFLZ and BMIZ were more strongly associated with FM than with FFM, whereas WFAZ correlated similarly with the 2 components of body composition. DWFLZ and DBMIZ were both more strongly related to DFM than to DFFM; however, a direct comparison of the 2 indexes with respect to change in the percentage of FM indicated that DBMIZ was the optimal proxy of adiposity gain (P , 0.0001, pairwise difference). Conclusions: Weight-and length-based indexes are poor surrogates for newborn adiposity. However, at 5 mo, WFLZ and BMIZ are suitable proxies of FM. When assessing adiposity gain, DBMIZ is the best indicator of fat accrual during the first 5 postnatal months. This trial was registered at clinicaltrials.gov as NCT02273297.Am J Clin Nutr 2017;106:559-67.