Abstract Background Due to difficulties in performing direct measurements as an exposure assessment technique, evidence supporting an association between physical exposures such as neck and shoulder muscle activities and postures and musculoskeletal disorders during computer use is limited. Alternative exposure assessment techniques are needed. Methods We predicted the median and range of amplitude (90^th-10^th percentiles) of trapezius muscle activity and the median and range of motion (90^th-10^th percentiles) of shoulder, head, neck, and torso postures based on two sets of parameters: the distribution of keyboard/mouse/idle activities only (“task-based” predictions), and a comprehensive set of task, questionnaire, workstation, and anthropometric parameters (“expanded model” predictions). We compared the task-based and expanded model predictions based on R² values, root mean squared (RMS) errors, and relative RMS errors calculated compared to direct measurements. Results The expanded model predictions of the median and range of amplitude of trapezius muscle activity had consistently better R² values (range 0.40-0.55 compared to 0.00-0.06), RMS errors (range 2-3%MVC compared to 3-4%MVC), and relative RMS errors (range 10-14%MVC compared to 16-19%MVC) than the task-based predictions. The expanded model predictions of the median and range of amplitude of postures also had consistently better R² values (range 0.22-0.58 compared to 0.00-0.35), RMS errors (range 2–14 degrees compared to 3–22 degrees), and relative RMS errors (range 9–21 degrees compared to 13–42 degrees) than the task-based predictions. Conclusions The variation in physical exposures across users performing the same task is large, especially in comparison to the variation across tasks. Thus, expanded model predictions of physical exposures during computer use should be used rather than task-based predictions to improve exposure assessment for future epidemiological studies. Clinically, this finding also indicates that computer users will have differences in their physical exposures even when performing the same tasks.