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This review assessed the efficacy and safety of nonprescription analgesics, including paracetamol (acetaminophen), metamizole and nonsteroidal anti\u2010inflammatory drugs (NSAIDs) used in combination <jats:italic>vs<\/jats:italic>. monotherapy in acute pain conditions. A literature search identified 25 studies that compared oral paracetamol combined with a nonprescription NSAID (oral or topical) <jats:italic>vs<\/jats:italic>. either or both components alone in an acute pain condition or in an acute episode or exacerbation of a chronic pain condition. Combination therapy provided superior pain relief <jats:italic>vs<\/jats:italic>. monotherapy in the dental impaction pain model; potential dose\u2010sparing and opioid\u2010sparing effects were also evident. After endodontic surgery, combination therapy provided greater pain relief <jats:italic>vs<\/jats:italic>. either component alone following a single dose, but a difference was not apparent with multiple dosing, indicating a faster onset of action with combination therapy. Studies in acute musculoskeletal pain yielded mixed results. Studies in patients with headache included caffeine in addition to paracetamol\/NSAIDs and showed that this combination provided faster and more effective pain relief <jats:italic>vs<\/jats:italic>. paracetamol or an NSAID alone. Across all settings, oral combination therapy with paracetamol\/NSAIDs was well tolerated, with adverse event rates similar to or even lower than those observed with monotherapy. Findings of this narrative review support the use of combination therapy with paracetamol and an NSAID in the postsurgical setting but not in acute non\u2013low\u2010back musculoskeletal pain. 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