BACKGROUND: Labour is a normal physiological process, but is usually associated with pain and discomfort. Numerous methods are used to relieve labour pain. These include pharmacological (e.g. epidural, opioids, inhaled analgesia) and non-pharmacological (e.g. hypnosis, acupuncture) methods of pain management. Non-opioid drugs are a pharmacological method used to control mild to moderate pain. OBJECTIVES: To summarise the evidence regarding the effects and safety of the use of non-opioid drugs to relieve pain in labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) using non-opioid drugs (non-steroidal anti-inflammatory drugs (NSAIDs); paracetamol; antispasmodics; sedatives and antihistamines) in comparison with placebo or standard care; different forms of non-opioid drugs (e.g. sedatives versus antihistamines); or different interventions (e.g. non-opioids versus opioids) for women in labour. Quasi-RCTs and trials using a cross-over design were not included. Cluster-randomised RCTs were eligible for inclusion but none were identified for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion all studies identified by the search strategy, carried out data extraction and assessed risk of bias. We resolved any disagreement through discussion with a third author. Data were checked for accuracy. MAIN RESULTS: Nineteen studies randomising a total of 2863 women were included in this review. There were three main comparison groups: 15 studies compared non-opioid drugs with placebo or no treatment (2133 women); three studies compared non-opioid drugs with opioids (563 women); and three studies compared one type of non-opioid drug with a different type or dose of non-opioid drug (590 women). Some of the studies included three or more groups and so have been put in more than one comparison. Overall, there was little difference between groups for most of the comparisons. Any differences observed for outcomes were mainly limited to one or two studies. Non-opioid drugs (sedatives) were found to offer better pain relief (mean difference (MD) -22.00; 95% confidence interval (CI) -35.86 to -8.14, one trial, 50 women), better satisfaction with pain relief (sedatives and antihistamines) (risk ratio (RR) 1.59; 95% CI 1.15 to 2.21, two trials, 204 women; RR 1.80; 95% CI 1.16 to 2.79, one trial, 223 women) and better satisfaction with the childbirth experience (RR 2.16; 95% CI 1.34 to 3.47, one trial, 40 women) when compared with placebo or no treatment. However, women having non-opioid drugs (NSAIDs or antihistamines) were less likely to be satisfied with pain relief compared with women having opioids (RR 0.50; 95% CI 0.27 to 0.94, one trial, 76 women; RR 0.73; 95% CI 0.54 to 0.98, one trial, 223 women). Women receiving the antihistamine hydroxyzine were more likely to express satisfaction with pain relief compared with the antihistamine promethazine (RR 1.21; 95% CI 1.02 to 1.43, one trial, 289 women). Women receiving sedatives were more likely to express satisfaction with pain relief compared with antihistamines (RR 1.52; 95% CI 1.06 to 2.17, one study, 157 women). The majority of studies were conducted over 30 years ago. The studies were at unclear risk of bias for most of the quality domains.Opioids appear to be superior to non-opioids in satisfaction with pain relief, while non-opioids appear to be superior to placebo for pain relief and satisfaction with the childbirth experience. There were little data and no evidence of a significant difference for any of the comparisons of non-opioids for safety outcomes. AUTHORS' CONCLUSIONS: Overall, the findings of this review demonstrated insufficient evidence to support a role for non-opioid drugs on their own to manage pain during labour.