A controlled, randomized, double-blind crossover study, in which the patients acted as their own controls, was carried out to test the efficacy of naproxen 500 mg × 2 versus acetaminophen 1000 mg × 4 for 3 days on the postoperative course following third molar surgery. Acetaminophen reduced the mean swelling on the 3rd postoperative day by 22.4% (p = 0.023) compared to that after naproxen. On the 6th postoperative day, there was 20.9% less mean swelling with naproxen (p = 0.44), although the total swelling measurements were much less than those measured on the 3rd postoperative day. Summed pain intensity (SUMPI3.5–11) on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen regimen with the exception of 0.5 hours (p = 0.002) and 1 hour (p = 0.009) after first medication when acetaminophen gave less pain than naproxen. Since the drug regimens were different, summed PI for the first acetaminophen dose interval (SUMPI3.5–6) and the first naproxen dose interval (SUMPI3.5–9) was calculated. There was a tendency toward a statistically significant difference in favor of acetaminophen for SUMPI3.5–6 (p = 0.055) but no statistically significant difference (p = 0.41) between the treatments with respect to SUMPI3.5–9. Naproxen was statistically superior (p ≤ 0.002) to acetaminophen at 08:00, 12:00, and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day, when the pain intensity level was lower than that on the day of surgery. A 3-day acetaminophen regimen reduces acute postoperative swelling better than naproxen on the 3rd postoperative day after third molar surgery but not on the 6th postoperative day when the total swelling is less.