This study addresses kinetic parameter estimation for a high-density polyethylene (HDPE) slurry process based on fitting molecular weight distributions (MWDs). From the process model, we conduct an estimability analysis by assessing the relative sensitivity between output variables and kinetic parameters as well as confidence intervals. This determines which parameters can be estimated. Conversely, a major challenge remains with the solution of an ill-conditioned parameter estimation problem with MWD as the output variable. To overcome the convergence difficulties with the associated problem, we develop a novel multistep methodology where we first obtain MWD parameters by matching to data and then estimate kinetic parameters by matching to the regressed MWD parameters. Computational results and eigenvalue analysis show this multistep methodology separates an ill-conditioned problem into two well-conditioned subproblems. Moreover, we consider simulation-based and industrial HDPE case studies. These results demonstrate the applicability, potential, and efficiency of this solution procedure. (c) 2014 American Institute of Chemical Engineers AIChE J, 60: 3442-3459, 2014