IR lasers are widely used in electro-optical applications, especially in detector characterization systems. These lasers can be extremely sensitive to fluctuations in the operational temperature of their cavity and other environmental factors. Due to these influences, the laser output signal normally fluctuates randomly. These variations make it difficult to characterize the laser waist position and exact focus, which in turn causes difficulty with detector measurement. We apply a multivariate statistical approach to characterize and filter these variations and to calculate the “best focus” of a carbon dioxide laser operating at 10.6 μm. Using this method, the “best focus” can be calculated with great accuracy and can be easily implemented during postsignal processing. Also, this technique can potentially be applied to other situations in which laser signal instability is significant. © 2005 Society of Photo-Optical Instrumentation Engineers.