The popularity of soft tissue fillers is, in part, due to their favorable side-effect profile. However, serious complications can occur. The authors describe their extensive clinical experience with soft-tissue augmentation and the rare complication of vascular compromise, which can lead to necrosis and scarring. Over a 10-year period between January 2003 and January 2013, the authors observed a total of 12 cases of vascular compromise. Eight patients in their clinical practice showed evidence of vascular compromise out of a total of 14,355 filler injections (0.05%). In addition, four patients treated with an experimental particulate filler had vascular complications. All cases were examined for filler type, location of complication, risk factors, treatment, and outcomes. Although treatment plans differed for each patient in their series, all cases of vascular compromise resolved fully. The authors believe that an office-based protocol for both immediate and ongoing care-including a thorough individualized assessment and treatment plan for each patient-is critical to timely and effective resolution of side effects. They propose key recommendations for the prevention and management of vascular compromise to improve patient outcomes and reduce the risk of permanent complications.