ObjectiveTo measure inter-protocol agreement and analyze interchangeability on nodule classification between low-dose unenhanced CT and standard-dose enhanced CT.Materials and MethodsFrom nodule libraries containing both low-dose unenhanced and standard-dose enhanced CT, 80 solid and 80 subsolid (40 part-solid, 40 non-solid) nodules of 135 patients were selected. Five thoracic radiologists categorized each nodule into solid, part-solid or non-solid. Inter-protocol agreement between low-dose unenhanced and standard-dose enhanced images was measured by pooling κ values for classification into two (solid, subsolid) and three (solid, part-solid, non-solid) categories. Interchangeability between low-dose unenhanced and standard-dose enhanced CT for the classification into two categories was assessed using a pre-defined equivalence limit of 8 percent.ResultsInter-protocol agreement for the classification into two categories {κ, 0.96 (95% confidence interval [CI], 0.94–0.98)} and that into three categories (κ, 0.88 [95% CI, 0.85–0.92]) was considerably high. The probability of agreement between readers with standard-dose enhanced CT was 95.6% (95% CI, 94.5–96.6%), and that between low-dose unenhanced and standard–dose enhanced CT was 95.4% (95% CI, 94.7–96.0%). The difference between the two proportions was 0.25% (95% CI, −0.85–1.5%), wherein the upper bound CI was markedly below 8 percent.ConclusionInter-protocol agreement for nodule classification was considerably high. Low-dose unenhanced CT can be used interchangeably with standard-dose enhanced CT for nodule classification.