Multiple image averaging (MIA) is a new approach to improve OCT angiography (OCTA) imaging. The aim of this work was to analyze the impact of MIA on image quality and quantitative OCTA parameters. Twenty eyes from 20 healthy volunteers (55.65 ± 14.8 years) were prospectively enrolled. Imaging was performed using two commercially available OCTA devices (Canon OCT HS-100, Optovue AngioVue) using a uniform imaging protocol. Each participant had two single scans of the macula (3 × 3mm, Canon and Optovue) as well as five continuous single scan imaging procedures (3 × 3mm each) using the Canon device. Three out of five of these images with highest quality were manually chosen and then automatically processed by the Canon device using MIA. The superficial retinal plexus of the single scans and of MIA images was analyzed with regard to the device' own image quality scores (IQS), peak signal-to-noise ratio (PSNR), the size of the foveolar avascular zone (FAZ), and vessel density (VD). Image acquisition times were recorded. Parameters were compared between the devices and the different imaging protocols. Average acquisition time was significantly higher for the MIA compared with the single measurements (29.09 ± 10.19 seconds (s) (MIA) vs. 5.56 ± 2.17 s (Canon single scan) vs. 20.28 ± 6.81 s (Optovue) (p < 0.001)). IQS showed no significant differences between the devices and between the recording protocols. PSNR was 12.38 ± 0.20 (Canon single scan), 13.01 ± 0.36 (Canon MIA), and 14.34 ± 0.60 (Optovue) (p < 0.001 between the groups). Mean FAZ area in Canon single scans was 0.29 ± 0.06 mm2, 0.27 ± 0.07 mm2 using MIA, and 0.27 ± 0.08 mm2 using the Optovue device. There was no significant difference between mean FAZ measurements before and after averaging (Canon single scan vs. MIA, p = 0.168). VD of the parafoveal area using MIA was significantly lower compared with both single scans (p < 0.001). MIA can improve PSNR, but it also reduces imaging speed and significantly affects VD measurements. Therefore, when comparing OCTA data, the use of uniform imaging protocols is required.