Purpose: The current study examined the validity of scores from the sitting time item on the International Physical Activity Questionnaire-Short Form (IPAQ-SF) in a sample of persons with multiple sclerosis (MS). Method: Persons with MS were recruited through the distribution of printed letters to a random sample of 1,000 persons from the North American Research Committee on MS registry. Two hundred ninety-five persons with MS were interested and volunteered to wear an ActiGraph accelerometer for a 7-day period and complete a battery of questionnaires that included the IPAQ-SF and Godin Leisure-Time Exercise Questionnaire over this period of time. Results: IPAQ-SF sitting time scores were consistently and moderately correlated with all of the sedentary behavior metrics from the accelerometer (range of r between .295 and .431), and the correlations were stronger than those between self-reported physical activity and sedentary metrics from the accelerometer (range of r between -.087 and .163). The correlations between IPAQ-SF sitting time scores with the accelerometer-derived sedentary behavior metrics were still statistically significant in the analyses controlling for physical activity (range of parametric correlations between .281 and .411). Conclusions: The correlation analysis indicated consistent, moderate correlations between IPAQ-SF sitting time scores and device-measured estimates of both the volume and pattern of sedentary behavior, and the correlations were (a) stronger than those for self-reported physical activity and (b) independent of self-reported physical activity. Such results provide initial evidence for the validity of inferences from IPAQ-SF sitting time scores as an overall measure of sedentary behavior in persons with MS.