According to one aspect of the teachings herein, a method and apparatus detect mechanical misalignments in a machine vision system during run-time operation of the machine vision system, and compensate image processing based on the detected misalignments, unless the detected misalignments are excessive. Excessive misalignments may be detected by determining a worst-case error based on them. If the worst-case error exceeds a defined limit, the machine vision system transitions to a fault state. The fault state may include disrupting operation of a hazardous machine or performing one or more other fault-state operations. Among the detected misalignments are internal misalignments within individual cameras used for imaging, and relative misalignments between cameras. The method and apparatus may further perform run-time verifications of focus and transition the machine vision system to a fault state responsive to detecting insufficient focal quality.