Systems for determining fractional flow reserve are disclosed. An example system may include a pressure sensing guidewire for measuring a first pressure, a second pressure sensing medical device for measuring a second pressure, and a processor coupled to the pressure sensing guidewire and coupled to the second pressure sensing medical device. The processor may be designed to generate a plot of the magnitude of the second pressure over time, identify one or more time intervals of the plot that have a slope less than zero, determine a mean of the second pressure, and calculate the ratio of the first pressure to the second pressure when (a) the second pressure is less than or equal to the mean of the second pressure and (b) during the one or more time intervals when the slope of the plot is less than zero.
