Note: Depending on where you live paracetamol is also known as acetaminophen, APAP and Tylenol. I have had a version of the following conversation a surprising number of times: > "I have a headache." > > "Aah, that sucks. Did you take some paracetamol?" > > "Yes, but it still hurts." > > "How many did you take?" The fact that I even ask this question is because I have been noticing a trend. > "One." > > "You should take two, it makes a big difference." > > "Nah, I'm fine with one." > > "But you still have a headache." > > "Yeah, but it doesn't make much of a difference. Paracetamol just doesn't work that well for me." Everyone is free to choose how many paracetamol they take, but I've always had this hunch that there is a big difference between taking one or two paracetamol. Where taking one has almost no effect on my headaches, but taking two makes a big difference. Effectively I'm making two claims: 1. 1000mg paracetamol works better than 500mg paracetamol. 2. 500mg paracetamol doesn't work much better than placebo. Today I chose to finally resolve this mystery and laugh in the face of my friends! Or I will admit in shame that I was wrong... Claim 2: 500mg vs placebo There is a Cochrane Review from 2016 that tries to answer exactly my question.[1] The review looks at pain relief with paracetamol for tension-type headaches, the most common form of headaches. They reference two studies that have compared 500mg/650mg with placebo that also fit their inclusion criteria. Steiner 2003[2], which comes to the following conclusion: They didn't find a significant result when comparing 500mg paracetamol and placebo! But they did find a significant result when comparing 1000mg paracetamol and placebo. Dahlöf 1996 is less conclusive. This study only contains 29 participants, where only 14 of them took paracetamol at a dose of 500mg. In this study both 500mg and 1000mg performed equally well, but with the low participant numbers it is hard to draw any