The effect of simulated breath flow rate, vapor temperature, and flow duration on the linearity and variation in the current response of an enzymatic electrochemical breath acetone sensor was examined. Variable simulated flow rate and vapor temperature only slightly increased the variation in the overall sensor current response to vapor acetone, while the response remained linear with acetone concentration. This increased variation was measured by a slightly decreased linear R2 compared to simulated breath under constant control conditions. Simulated variable flow duration increased the variation in sensor response, especially for blow times less than 5 s at vapor acetone concentrations less than 1 ppm (v/v). This trend with flow duration was reflected in data produced during human breath testing. In all cases, the sensor current response remained linear with vapor acetone concentration. In a clinical test, the sensor current displayed a linear dependence on human breath acetone concentrations ranging from 0.2 to 17 ppm (v/v), as measured by gas chromatography. The linear R2 across 201 direct human breath measurements was 0.949.