The New Zealand Building Code is unique in the world in requiring evidence of a minimum durability of 50 years for all structural building elements. This prescriptive durability requirement equally applies to the adhesives used in structural applications such as engineered wood products (EWPs), including glulam, CLT and LVL. Conventional resorcinol-based structural adhesives have a long history of use in New Zealand, providing evidence of their ability to meet stringent durability requirements. Structural adhesives based on polyurethanes (PURs) are used extensively in other parts of the world and are rapidly gaining increasing interest in New Zealand due to their perceived environmental and production advantages. However, without a sufficiently long history of use, and a lack of data around their performance in the preservative treated pine EWPs typically manufactured in New Zealand, it is difficult to provide evidence of long-term durability for PURs in our domestic building industry. In this work, attenuated total reflectance Fourier transform infrared (ATR FTIR) spectroscopy in conjunction with multi-component analysis (chemometrics) was used to understand the changes that accelerated ageing cause in the chemistry of five PUR-based adhesives. The effect of hygrothermal stress was investigated through exposure of samples to accelerated ageing cycles of varying temperatures and humidities for up to 3 years’ duration. Different samples were affected to different extents by each cycle. Spectroscopic data were also used to build predictive models which have the potential to be used in long-term durability assessment. Spectroscopic investigation in conjunction with mechanical testing offers the opportunity to provide a robust, fit-for-purpose test methodology for assessing the long-term durability of PUR-based structural adhesives.