Electronic pedometers are relatively inexpensive devices to monitor physical activity. To assess physical activity intensity using a pedometer, establishing the relationship between step-rate measured by a pedometer and the rate of oxygen uptake (VO[subscript 2]) is needed. This study examined the step-counting accuracy of the NL-2000i electronic pedometer and whether pedometer-measured step-rate accurately predicts the energy expenditure in adults with and without Down syndrome (DS). Participants were 15 adults with DS and 15 adults without DS. Participants completed three walking trials at: their preferred speed; 0.8 m·s[superscript -1]; and 1.4 m·s[superscript -1]. We measured VO[subscript 2] with a portable open-circuit spirometer and step rate with NL-2000i worn on the non-dominant hip and hand-tally as the criterion. We used multi-level modeling to develop an equation predicting VO[subscript 2]. We computed the absolute percent error of the VO[subscript 2] prediction equation and the step-counting error of the pedometer. We evaluated differences between groups across speeds for these variables using 2 × 3 (group × speed) two-way analysis of variance. Step-counting error of the NL-2000i was low, but it was higher in adults with than without DS at the preferred and fast walking speeds (p[less than or equal to] 0.029). An equation predicting energy expenditure included step-rate, group, and their interaction (p < 0.001; R[superscript 2] = 0.52). The NL-2000i pedometer has high accuracy across speeds. Step-rate measured by NL-2000i predicts energy expenditure with a relatively low error in adults with and without DS.