To describe circadian blood pressure (BP) patterns and linear interdialytic changes, a model was developed to describe simultaneously both the straight line change and oscillatory variation in BP and heart rate over an interdialytic interval in hemodialysis patients. Using this trended cosinor model, we simultaneously compared the impact of mean level of BP, linear changes over the interdialytic interval, and oscillatory changes in BP and its relationship with antihypertensive drug use. Neither a straight-line change model nor the cosinor model adequately described the BP variability in 12,750 BP measurements from 136 chronic stable hemodialysis patients. A combination of the 2 models that allowed for the oscillatory rhythmic pattern in BP variation to have an upward trend in the interdialytic period most accurately described the data. Time elapsed since the end of dialysis demonstrated a better model fit compared with the less meaningful clock time. More antihypertensive medication use was associated with increasing mean systolic, diastolic, and pulse pressure. Although the rate of change was blunted with increasing antihypertensive drug use, the impact on oscillatory change was U-shaped for systolic BP, direct for diastolic BP, and inverse for pulse pressure. A trended cosinor model better describes the change in BP in the interdialytic interval in hemodialysis patients, especially when time elapsed is measured from the end of dialysis. Antihypertensive drugs, though associated with higher average BP, are associated with blunted rate of change in BP over time.