Before anything else, please check one thing, because it decides the rest: the processor architecture of the machine. XLS Padlock protected applications require 64-bit Windows on an Intel or AMD (x64) processor. They do not currently support Windows on ARM, and on an ARM machine the protection layer's startup self-check can fail with exactly this "The operating system is not presently configured to run this application" message.
I put this first because you also asked about running on a Mac. If this Windows is Windows on ARM, for example Windows 11 on ARM inside Parallels, VMware Fusion, or UTM on an Apple Silicon (M-series) Mac, or on an ARM device such as a Snapdragon or Copilot+ PC, then the app is running under ARM emulation, and that is the most likely cause here rather than a setting you can change.
How to check: open Settings, then System, then About, and look at "System type".
- If it reads "ARM-based processor", that is the cause. The protected app is not supported on Windows on ARM at the moment, it needs to run on a real x64 Windows machine (a normal Intel or AMD PC). The fact that it sometimes starts on a second try does not make ARM a supported target, the self-check is simply not reliable there.
- If it reads "x64-based processor", the architecture is fine and we look at the environment instead, below.
If you are on x64 Windows, the usual cause of this exact message is antivirus or endpoint-security software interfering with the freshly extracted protected code as it starts. That fits the "works on the next run" behaviour, and it is fixable:
- Antivirus and Defender: add exclusions for the folder the .exe runs from, and on your build machine for the XLS Padlock installation folder and XLSPadlockDesigner.exe. Check Windows Security, Virus and threat protection, Protection history for anything removed or blocked that points at your .exe. On managed PCs, attack-surface-reduction and anti-exploit rules that block Office-related process injection are a frequent trigger.
- Run location: launch the .exe from a normal local folder such as C:\Temp, not from a cloud-synced folder (OneDrive, Dropbox, Google Drive) or a network drive.
- Latest build: we released XLS Padlock 2026.1 today, which hardens the embedded runtime. If your maintenance is active it is a free upgrade, so update, rebuild, and redistribute.
To point you the right way, could you tell us:
- The System type from Settings, System, About (ARM-based, or x64-based).
- Your exact XLS Padlock version and build (Help, then About).
- Whether it happens on one machine or several, and which antivirus or security suite runs on the affected machine.
