An auto-calibrating pneumatic compression therapy device configured for compression therapy, the device comprising: an inflatable compression sleeve comprising an inflatable cell, a fill manifold configurable to be in fluid communication with the inflatable cell, a fluid source having a source output configured to introduce a fluid into the inflatable cell via the fill manifold, a fill valve positioned between the fluid source and fill manifold that is configured to moderate fluid output from the fluid source into the fill manifold, a cell valve disposed between the inflatable cell and the fill manifold configured to moderate fluid flow from the fill manifold into the inflatable cell, an exhaust valve that can be closed when the fill valve opens, a pressure sensor, and a controller configured to receive pressure sensor data from the pressure sensor, and to control actions of the fill valve, cell valve and the fluid source, the controller comprising at least one processor device and at least one non-transitory memory storage device; wherein the controller is adapted: to receive, when the inflatable cell receives a first portion of fluid from the fluid source, dynamic pressure sensor data related to a dynamic pressure within the fill manifold and/or inflatable cell, to close the fill valve to prevent fluid output into the fill manifold and subsequently to receive static pressure sensor data related to a static pressure within the fill manifold and/or inflatable cell, when the exhaust valve is closed, to calculate a pressure difference between the dynamic pressure sensor data and the static pressure sensor data, and to calibrate a dynamic pressure sensor target value based, at least in part, on one or more of a static pressure sensor target value, the dynamic pressure sensor data, the static pressure sensor data, and the pressure difference. an inflatable compression sleeve comprising an inflatable cell, a fill manifold configurable to be in fluid communication with the inflatable cell, a fluid source having a source output configured to introduce a fluid into the inflatable cell via the fill manifold, a fill valve positioned between the fluid source and fill manifold that is configured to moderate fluid output from the fluid source into the fill manifold, a cell valve disposed between the inflatable cell and the fill manifold configured to moderate fluid flow from the fill manifold into the inflatable cell, an exhaust valve that can be closed when the fill valve opens, a pressure sensor, and a controller configured to receive pressure sensor data from the pressure sensor, and to control actions of the fill valve, cell valve and the fluid source, the controller comprising at least one processor device and at least one non-transitory memory storage device; wherein the controller is adapted: to receive, when the inflatable cell receives a first portion of fluid from the fluid source, dynamic pressure sensor data related to a dynamic pressure within the fill manifold and/or inflatable cell, to close the fill valve to prevent fluid output into the fill manifold and subsequently to receive static pressure sensor data related to a static pressure within the fill manifold and/or inflatable cell, when the exhaust valve is closed, to calculate a pressure difference between the dynamic pressure sensor data and the static pressure sensor data, and to calibrate a dynamic pressure sensor target value based, at least in part, on one or more of a static pressure sensor target value, the dynamic pressure sensor data, the static pressure sensor data, and the pressure difference. to receive, when the inflatable cell receives a first portion of fluid from the fluid source, dynamic pressure sensor data related to a dynamic pressure within the fill manifold and/or inflatable cell, to close the fill valve to prevent fluid output into the fill manifold and subsequently to receive static pressure sensor data related to a static pressure within the fill manifold and/or inflatable cell, when the exhaust valve is closed, to calculate a pressure difference between the dynamic pressure sensor data and the static pressure sensor data, and to calibrate a dynamic pressure sensor target value based, at least in part, on one or more of a static pressure sensor target value, the dynamic pressure sensor data, the static pressure sensor data, and the pressure difference.