Water uptake influences many properties of polymers and has been widely studied. In the context of polymeric biomaterials, several publications reported an unusual high variability of analytical results, without further investigating the cause for this phenomenon. Using selected polymers from the library of L-tyrosine-derived polyarylates and poly(D,L lactic acid), we showed that nonaged and nonannealed compression molded film samples exhibit the typical large variation in water uptake observed in previous reports. The introduction of an annealing step allows accurate and reproducible water uptake measurements for these polymers. We evaluated the use of 3 H-radiolabeled water for the determination of water uptake, finding that the use of radiolabeled water yields statistically indistinguishable measurements, compared to gravimetric methods, while providing significant advantages in throughput and sensitivity. Using the recommended methods of annealing and (3)H-radiolabled water, the water uptake profiles of 24 polymers of the library of L-tyrosine-derived polyarylates are reported. This article addresses experimental concerns related to water uptake studies and may assist other researchers in improving the accuracy of their water uptake results. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 1311-1320, 2011