PURPOSE: To characterize the types and frequencies of image artifacts associated with macular scanning using 2 common spectral-domain optical coherence tomography (SD OCT) instruments and to evaluate the impact of artifacts on foveal thickness measurements. DESIGN: Retrospective, observational chart review. PARTICIPANTS: For the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA), scans of 98 eyes from 58 patients were included in the study. For the Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany), scans of 88 eyes from 54 patients were included. METHODS: Macular volume scans of healthy and diseased eyes were evaluated systematically for image artifacts within each scan overall and within the center 1-mm area. The frequency of each artifact type was compared for scans stratified by diagnosis category. Artifacts in the center 1-mm area were graded for severity and were corrected manually using each instrument's software. Artifacts that resulted in errors of more than 50 microm or more than 10% of retinal thickness or that caused a misdiagnosis of macular edema or retinal thinning were defined as clinically significant and were analyzed further. MAIN OUTCOME MEASURES: Overall frequency of image artifacts by artifact type, relative frequency of artifacts in scans stratified by posterior segment disease diagnosis, and retinal thickness measurements of the center 1-mm subfield before and after artifact corrections. RESULTS: For Cirrus, 84.7% of scans had artifacts and 32.7% had at least 1 artifact in the center 1-mm area of the scan. For Spectralis, 90.9% of scans had at least 1 artifact, and 37.5% had at least 1 artifact in the center 1-mm area. Certain artifact types were observed more frequently with specific disease states. Clinically significant artifacts involving the center 1-mm area were seen in 5.1% of Cirrus and 8.0% of Spectralis scans. CONCLUSIONS: Image artifacts in SD OCT volume scanning are common and frequently involve segmentation errors. Artifacts are relatively less common in the center 1-mm area of scans, but may affect retinal thickness measurements in a clinically significant manner. Careful review of scans for artifacts is important when using SD OCT images and retinal thickness measurements in patient care or clinical trials.