(1) Background: Multiple point-of-care (POC) glucometers are in use in veterinary medicine, but few are compared to each other. This leaves the potential for clinicians to be unaware of the effect of bias when comparing results from different POC glucometers. (2) Methods: Samples from healthy calves and ewes were simultaneously compared with two POC veterinary glucometers, the Precision Xtra and the AlphaTrak2, under both the “canine” and “feline” settings. The results of each sample were statistically analyzed with linear regression and Bland–Altman analysis. (3) Results: 170 samples from healthy calves and 108 samples from healthy ewes were available for comparison. Calves: The AT2 consistently overestimated blood glucose concentrations when compared to the PX device with the calves. Correlationt with the PX was r = 0.8496 (canine setting) and r = 0.8861 (feline setting). Both the canine and feline settings demonstrated a consistent bias (41.11 and 33.64 mg/dL, respectively). Ewes: The AT2 consistently overestimated blood glucose concentrations when compared to the PX device with the ewes. Correlation with the PX was R = 0.4710 (canine setting) and R = 0.7269 (feline setting). Both the canine and feline settings demonstrated a consistent bias (21.23 and 14.54 mg/dL, respectively). (4) Clinicians should be aware of the potential for consistent bias when evaluating calf and sheep blood glucose concentrations as the AT2 device, at both settings, overestimated blood glucose compared to the previously validated PX. This reliability appears to change when the values are farther from the normal ranges, which should be considered when making clinical decisions based on data from these devices.
