Countless inputs are used in transient hygrothermal analysis, just as countless variables determine the long-term hygrothermal performance of a real-world building envelope assembly. One variable often overlooked, oversimplified, and inaccurately accounted for is the initial moisture content of materials. This paper discusses the impact initial moisture content has on both the real-world performance and the accuracy of the modeled hygrothermal performance. ASHRAE Standard 160, Criteria for Moisture-Control Design Analysis in Buildings, provides guidelines for assumptions of initial moisture content inputs in hygrothermal analysis. These guidelines are generic in nature and are not necessarily representative of in-service conditions. The authors conducted a study to explore the role that a range of inputs have on the accuracy of hygrothermal models. Temperature and humidity data across a wall assembly along with all necessary interior and exterior climate data were collected over the course of several seasons. The data were used to develop a series of WUFI models, attempting to validate these models and the default or recommended inputs. The study indicated that the models did not accurately reflect the data recorded in the field unless values for the initial moisture content matched what was recorded in the field rather than the default ASHRAE 160 recommended values. This study, and several other real-world cases where excessive initial moisture content has led to envelope failures, highlights the importance of accurately accounting for initial moisture content. Particularly in the cases of renovations and restoration projects, methods are available to determine realistic values of the initial moisture content within the existing materials. Appropriate methods for determining the initial moisture content of materials comprising existing envelope assemblies are discussed, including the methods contained within the new standard ASTM E3069-19, Standard Guide for Evaluation and Rehabilitation of Mass Masonry Walls for Changes to Thermal and Moisture Properties of the Wall.