The aim of this study is to develop a combined experimental and analytical framework for accelerated lifetime estimates of semi-crystalline plastic pipes which is sensitive to changes in structure, orientation, and morphology introduced by processing conditions. To accomplish this task, high-density polyethylene (HDPE) is chosen as the exemplary base material. As a new accelerated test protocol, several characterization tests were planned and conducted on as-manufactured HDPE pipe segments. Custom fixtures are designed and developed to admit uniaxial characterization tests. The yield behavior of the material was modeled using two hydrostatic pressure modified Eyring equations in parallel to describe the characterization test data collected in axial tension and compression. Subsequently, creep rupture failure of the pipes under hydrostatic pressure is predicted using the model. The model predictions are validated using the experimental creep rupture failure data collected from internal pressurization of pipes using a custom-designed, fully automatic test system. The results indicate that the method allows the prediction of pipe service lifetimes in excess of 50 years using experiments conducted over approximately 10 days instead of the traditional 13 months. The analytical model is joined with a commercial finite element package to allow simulations including different thermal-mechanical loading conditions as well as complicated geometries. The numerical model is validated using the characterization test data at different temperatures and deformation rates. The results suggest that the long-term performance of the pipe is dominated by the plastic behavior of the material and its viscoelastic response is found to play an insignificant role in this manner. Because of the potential role of residual stresses on the long-term behavior, the residual stress across the wall thickness is measured for three geometrically different HDPE pipes. As expected, the magnitude of tensile and compressive residual stresses are found to be greater in pipes with thicker walls. The effect of the residual stress on the long-term performance of the pipes is investigated by including the residual stress measurements into the numerical simulations. The residual stress slightly accelerates the failure process; however, for the pipe geometries examined, this acceleration is insignificant.