Paracetamol (acetaminophen) is the most commonly used analgesic medicine;1 because of its low cost and availability without prescription, it is the drug most frequently taken for self‐medication.2 The World Health Organization includes paracetamol in its list of essential medicines (“the most efficacious, safe and cost‐effective medicines for priority conditions”).3 The analgesic action of paracetamol has been attributed to its inhibition of the cyclooxygenase (COX) pathway in the central nervous system, reducing the production of pain‐mediating prostaglandins, but it may also enhance endocannabinoid transmission and modulate descending serotonergic inhibitory pathways.

4Clinical practice guidelines recommend regular, time‐limited use of Paracetamol for treating mild to moderate acute pain and chronic non‐malignant pain.5,6 Despite the widespread use of paracetamol, concerns have been expressed that it may be ineffective for treating painful conditions7 and perhaps less safe than previously thought.8 However, claims regarding the frequency and severity of adverse events are largely based on observational studies in which comparatively large therapeutic doses were consumed over long periods (eg, up to 4 g/day for four weeks8).

It has recently been suggested that paracetamol is ineffective or minimally effective for treating low back pain,9 leading to recommendations that non‐steroidal anti‐inflammatory drugs (NSAIDs) be used for initial pharmacological therapy.10 However, there are no published systematic reviews of the efficacy and safety of paracetamol across the broad range of conditions in which it is employed. Further, narrative reviews have included conflicting information, adding to uncertainty about its appropriate use.

Clinicians and patients need information about the efficacy and safety of paracetamol when deciding whether to use it. The aim of our umbrella systematic review was to provide a comprehensive overview of systematic reviews of the efficacy and safety of paracetamol as an analgesic in a range of painful conditions, particularly with respect to providing immediate relief.