The effectiveness of prochlorperazine buccal as an anti-emetic for the prevention of post-operative nausea and vomiting in patients using intravenous patient-controlled analgesia with morphine following abdominal hysterectomy has been assessed in a randomized, double-blind, placebo-controlled study. Forty-nine female patients participated with 26 allocated to the prochlorperazine buccal group and the remainder to the placebo group. Each received either placebo or prochlorperazine buccal 6 mg, in each case by the buccal route, 1 h prior to anaesthesia with further doses at 6, 18, 30 and 42 h, respectively. Symptom scores in respect of nausea, pain and sedation, the number without nausea, the number without vomiting and the requirement for rescue anti-emetic therapy were noted for each 4-h period during the 48-h study. Morphine utilization and taste associated with the study material were recorded. Data for 21 patients in the placebo group and 25 patients in the prochlorperazine buccal group were available for analysis. Patients in the prochlorperazine buccal group showed significantly lower mean nausea scores at 4–8 h (placebo group: mean nausea score 0.95; prochlorperazine buccal group: mean nausea score 0.36; P<0.05) and at 16–20 h (placebo group: mean nausea score 1.24; prochlorperazine buccal group: mean nausea score 0.48; P <0.05). Furthermore, the prochlorperazine buccal group showed significantly more patients without nausea at 4–8 h (placebo group: 11 patients out of 21; prochlorperazine buccal group: 20 patients out of 25; P<0.05) and at 16–20 h (placebo group: nine patients out of 21; prochlorperazine buccal group: 18 patients out of 25; P<0.05). The prochlorperazine buccal group showed a significantly higher number of patients rating the taste as unsatisfactory (placebo group: two patients out of 21; prochlorperazine buccal group: nine patients out of 25; P<0.05). Intravenous droperidol is the current gold standard prophylactic anti-emetic in post-operative nausea and vomiting associated with intravenous patient controlled analgesia with morphine usage. This study has demonstrated a peri-operative prochlorperazine buccal regimen to be effective in post-operative nausea and vomiting prophylaxis in the use of intravenous patient controlled analgesia with morphine. Prochlorperazine buccal should be considered as an effective, inexpensive option for the prevention of post-operative nausea and vomiting in post-operative intravenous patient controlled analgesia with morphine administration.