In current practice, diagnostic parameters, such as fractional flow reserve (FFR) and coronary flow reserve (CFR), are used to determine the severity of a coronary artery stenosis. FFR is defined as the ratio of hyperemic pressures distal () and proximal () to a stenosis. CFR is the ratio of flow at hyperemic and basal condition. Another diagnostic parameter suggested by our group is the pressure drop coefficient (CDP). CDP is defined as the ratio of the pressure drop across the stenosis to the upstream dynamic pressure. These parameters are evaluated by invasively measuring flow (CFR), pressure (FFR), or both (CDP) in a diseased artery using guidewire tipped with a sensor. Pathologic state of artery is indicated by lower CFR (<2). Similarly, FFR lower than 0.75 leads to clinical intervention. Cutoff for CDP is under investigation. Diameter and vascular condition influence both flow and pressure drop, and thus, their effect on FFR and CDP was studied. In vitro experiment coupled with pressure-flow relationships from human clinical data was used to simulate pathophysiologic conditions in two representative arterial diameters, 2.5 mm (N1) and 3 mm (N2). With a 0.014 in. (0.35 mm) guidewire inserted, diagnostic parameters were evaluated for mild (∼64% area stenosis (AS)), intermediate (∼80% AS), and severe (∼90% AS) stenosis for both N1 and N2 arteries, and between two conditions, with and without myocardial infarction (MI). Arterial diameter did not influence FFR for clinically relevant cases of mild and intermediate stenosis (difference < 5%). Stenosis severity was underestimated due to higher FFR (mild: ∼9%, intermediate: ∼ 20%, severe: ∼ 30%) for MI condition because of lower pressure drops, and this may affect clinical decision making. CDP varied with diameter (mild: ∼20%, intermediate: ∼24%, severe: by 2.5 times), and vascular condition (mild: ∼35%, intermediate: ∼14%, severe: ∼ 9%). However, nonoverlapping range of CDP allowed better delineation of stenosis severities irrespective of diameter and vascular condition.