It is challenging to predict crystallographic B-factors of a protein from a conventional molecular dynamics (MD) simulation. This is partly because the B-factors calculated through sampling the atomic positional fluctuations in a picosecond MD simulation are unreliable, and longer samplings often yield substantially large root mean square deviations (RMSDs) between calculated and experimental B-factors. This article reports the use of uniformly increased atomic masses by 100-fold to increase the time resolution of an MD simulation so that sampling the atomic positional fluctuations in multiple picosecond MD simulations with such high masses can improve the B-factor prediction. Using the third immunoglobulin-binding domain of protein G, bovine pancreatic trypsin inhibitor, ubiquitin, and lysozyme as model systems, the Cα and Cγ B-factor RMSDs of these proteins were ranging from 3.1±0.2 Å2 to 9.2±0.8 Å2 or from 3.6±0.1 Å2 to 9.6±0.2 Å2, respectively, when the sampling was done, for each of these proteins, in 20 distinct, independent, and 50-picosecond high-mass MD simulations using AMBER forcefield FF12MC or FF14SB. These results suggest that sampling the atomic positional fluctuations in multiple picosecond high-mass MD simulations may be conducive to a priori prediction of crystallographic B-factors of a folded protein.