Introduction The safety and efficacy of 1 or 2 tablets of extended-release hydrocodone 15 mg/acetaminophen 500 mg (HC/APAP CR) were evaluated following bunionectomy. Methods 163 patients recruited from 5 US sites were randomized to the following treatment groups: 2 placebo tablets (n=53), 1 tablet HC/APAP CR plus placebo (n= 54), or 2 tablets HC/APAP CR (n=56) at onset of moderate to severe pain. Patients were dosed every 12 hours for 48 hours (4 total doses), and after the first dose, were followed for 7 days [± 2]. The primary endpoint was time-interval weighted sum of pain intensity difference (SPID) over the first 12 hours, measured by visual analog scale (VAS), (higher scores indicate better pain relief). Time to onset of pain relief, one of several secondary endpoints, is also presented here. Patients received rescue medication as needed. Results 161/163 patients completed the study. Baseline variables were generally similar among groups. Most patients were female (89%); the mean age was 42.1 years. Patients receiving HC/APAP CR showed statistically significant improvement in all efficacy variables reported here, except 1-tablet HC/APAP CR for time to perceptible pain relief (Table 1). Incidence of adverse events was significantly higher for patients receiving HC/APAP CR versus placebo and for patients receiving 2-tablet HC/APAP CR versus 1 tablet. The most common adverse events were nausea, vomiting, somnolence, headache, dizziness, and pruritus. Conclusion One or 2 tablets of HC /APAP CR provided significantly better pain control as compared to placebo in subject with acute pain after bunionectomy. Additionally, two tablets provided consistently superior pain control to 1 tablet.