Both interfaces are faster than a typical 7200 RPM hard drive so it comes down mostly to compatibility. eSATA data rate is 3Gpbs and USB3 is 4.8Gbps but since USB3 requires a “bridge chip” to convert to native SATA anyway you actually see a small performance decrease on some USB3 connected systems (less than 5%). Some systems have difficulty with eSATA controller compatibility and for those we recommend trying USB3. For USB3 multibay models like the 5, 7, or 10 bay JBOD High-Rely classic family be aware that when swapping drives all drives go offline momentarily as a bus reset is done. This usually is not a problem unless multiple backups are underway when a media swap is done. the eSATA model doesn’t typically have this.