Objective To compare the efficacy of soluble aspirin 900 mg and paracetamol 1,000 mg in patients with postoperative pain after third molar surgery. Design A randomised, placebo controlled, double-blind study. Setting Day stay units of Oral and Maxillofacial Surgery at Cardiff Dental Hospital and Hexham General Hospital, Northumberland. Subjects and methods One hundred and sixty-seven (104 female) patients who required the removal of their impacted third molars under general anaesthesia. Intervention In the early postoperative period, patients were medicated with either a single dose of soluble aspirin 900 mg, solid paracetamol 1,000 mg or placebo. Main outcome measures Pain intensity was measured on 100 mm visual analogue scales at 0,5,10, 15, 20, 30, 45, 60, 90, 120 and 240 minutes after dosing. Other efficacy variables evaluated included time to rescue medication and an overall assessment of the study medication efficacy by the patient on completion of the study. Results One hundred and sixty-seven patients consented to take part in the study, but only 153 were medicated. Of the 14 patients not treated, 10 failed to develop sufficient pain to enter the study, two withdrew consent, one had an adverse reaction to the general anaesthetic and one was a protocol violator. Over the four hour investigation period, patients treated with soluble aspirin reported significantly less pain when compared with those treated with paracetamol (mean difference in AUC 0-240 = -2001, 95% CI -3893 to -109, p=0.038) and placebo (mean difference in AUC 0-240 = -3470, 95% CI -5719 to -1221, p=0.003).