The purpose of this study was to evaluate the measurement error and inter- and intra-observer variability of completely off-line automated and semi-automated carotid intima-media thickness (cIMT) measurement software (AtheroEdge™). Two hundred carotid ultrasound images from 50 asymptomatic women were analyzed. AtheroEdge™ was benchmarked against a commercial system (Syngo, Siemens) using automated and semi-automated modes. The measurement error and inter- and intra-observer variability of AtheroEdge™ were tested using three readings. The measurement error of AtheroEdge™ compared to the commercial software was 0.002±0.019mm (r=0.99) in the automated mode and -0.001±0.004mm in the semi-automated mode (r=0.99). The measurement error of AtheroEdge™ compared to the mean value of the three expert Readers (cIMT bias) for the automated and semi-automated methods was -0.0004±0.158mm and -0.008±0.157mm, respectively. The Figure-of-Merit was 99.8% and 99.9% when compared to the commercial ultrasound scanner (using the automated and semi-automated method, respectively) and was 99.9% and 98.9% when compared to the mean value of the three expert Readers. Regarding inter- and intra-observer variability, the intra-class correlation coefficient of the three independent users using the semi-automated AtheroEdge™ was 0.98. AtheroEdge™ showed a measurement performance comparable to the commercial ultrasound scanner software and the expert Readers' tracings. AtheroEdge™ belongs to a class of automated systems that could find application in processing large datasets for common carotid arteries, avoiding subjectivity in cIMT measurements.