This study focused on lower leg swelling as a typical physical load in prolonged sitting postures such as driving. We obtained prediction equations for lower leg swelling (ratio of the inverse of the measured impedance to the initial impedance and lower leg swelling assessment value, BI [%]) from thigh pressure distribution, participants’ physical characteristics, and sitting time. A total of 22 participants (11 males and 11 females) were recruited. The impedance in the lower leg and thigh pressure distribution were measured over 90 min in a sitting posture at three tilt angles (8°, 0°, and −8° from the horizontal plane). Multiple regression analysis was performed to construct prediction equations for lower leg swelling in the males, the females, and all the participants. Bioelectrical impedance was selected as the dependent variable, with height, body fat percentage, thigh pressure distribution, and sitting time as the independent variables. The validity of all constructed prediction equations for the males, the females, and all the participants was confirmed by an adjusted R2. These findings can be used to develop a device to prevent lower leg swelling (the main problem resulting from a prolonged sitting posture) and can be applied to automobile seats, aircraft seats, and office chairs.