A systematic review of the literature on the use of regional anesthesia (RA) and patient-controlled analgesia (PCA) was conducted in patients who require orthopedic extremity procedures to determine whether either analgesic technique contributes to a delayed diagnosis of compartment syndrome (CS). A total of 34 relevant articles (28 case reports and six research articles) were identified. Of all case report articles published after 2009, the majority (75%) concluded that RA does not put the patient at an increased risk of a delayed diagnosis of CS. Of these, only two relevant prospective research studies focusing on RA or PCA and their relationship to CS were identified. Neither study resulted in any cases of CS. However, both had relatively small sample sizes. Given the lack of evidence identified in this systematic review, prospective studies or large-scale retrospective data reviews are needed to more strongly advocate the use of one modality of analgesia over the other in this patient population.