Surgery in the prone position is often a necessity when access to posterior anatomic structures is required. However, many complications are known to be associated with this type of surgery, as physiologic changes occur with increased pressure to anterior structures. While several studies have discussed postoperative vision loss, much fewer studies with lower levels of evidence have addressed other complications. A systematic literature review was conducted using 2 different databases, and 53 papers were regarded as appropriate for inclusion. Qualitative and quantitative analysis was performed. Thirteen complications were identified. Postoperative vision loss and cardiovascular complications, including hypovolemia and cardiac arrest, had the most number of studies and highest level of evidence. Careful planning for optimal positioning, padding, timing, as well as increased vigilance are evidence-based recommendations where operative prone positioning is required.