PURPOSE OF REVIEW: An increasing amount of literature supports a multimodal approach to analgesic administration in the management of postoperative pain. The purpose of this study and review was to further evaluate the differences in efficacy in controlling immediate postoperative pain among the various routes of analgesia administration. RECENT FINDINGS: This study consisted of an analysis of the various routes of analgesic administration (parental, neuraxial, and oral/rectal) in 107,671 consecutive surgical cases performed over a 10-year period at Yale New Haven Hospital. This study included variables of postoperative pain score at initial request for analgesic, pain score at discharge, nausea and vomiting in the post-anesthesia care unit, and gender. The most common route of administration of analgesia in our study was via the parenteral route (29,962), and the least common route was the neuraxial route (1319). There was a significant decrease in pain scores at the time of discharge in all three groups relative to the pain score at first request for analgesia. Multimodal analgesia via various routes of administration targets numerous proponents of the nervous system with the intent to reduce the adverse side effects of the individual analgesics if given alone or as an additive to produce synergistic analgesia. Our study suggests that although all the routes investigated (parenteral, neuraxial (intrathecal/epidural), and per os or per rectum (PO/PR)) promote significant pain relief on discharge from the PACU, the group that received neuraxial analgesia reported the lowest incidence of nausea and vomiting.