Buildings consume more than one third of the world’s total primary energy. Weather plays a unique and significant role as it directly affects the thermal loads and thus energy performance of buildings. The traditional simulated energy performance using Typical Meteorological Year (TMY) weather data represents the building performance for a typical year, but not necessarily the average or typical long-term performance as buildings with different energy systems and designs respond differently to weather changes. Furthermore, the single-year TMY simulations do not provide a range of results that capture yearly variations due to changing weather, which is important for building energy management, and for performing risk assessments of energy efficiency investments. This paper employs large-scale building simulation (a total of 3162 runs) to study the weather impact on peak electricity demand and energy use with the 30-year (1980 to 2009) Actual Meteorological Year (AMY) weather data for three types of office buildings at two design efficiency levels, across all 17 ASHRAE climate zones. The simulated results using the AMY data are compared to those from the TMY3 data to determine and analyze the differences. Besides further demonstration, as done by other studies, that actual weather has a significant impact on both the peak electricity demand and energy use of buildings, the main findings from the current study include: 1) annual weather variation has a greater impact on the peak electricity demand than it does on energy use in buildings; 2) the simulated energy use using the TMY3 weather data is not necessarily representative of the average energy use over a long period, and the TMY3 results can be significantly higher or lower than those from the AMY data; 3) the weather impact is greater for buildings in colder climates than warmer climates; 4) the weather impact on the medium-sized office building was the greatest, followed by the large office and then the small office; and 5) simulated energy savings and peak demand reduction by energy conservation measures using the TMY3 weather data can be significantly underestimated or overestimated. It is crucial to run multi-decade simulations with AMY weather data to fully assess the impact of weather on the long-term performance of buildings, and to evaluate the energy savings potential of energy conservation measures for new and existing buildings from a life cycle perspective.