The findings deepen the mystery of the "placebo effect", showing there is more involved than mere positive thinking.
Until now, it had been thought patients responded to placebo drugs only when they believed them to be real.
The new US research shows this is not always the case. Participants experienced relief from irritable bowel syndrome (IBS) despite being told their medication was "like sugar pills" and contained no active ingredients.
At the end of a three-week trial, twice as many patients given the "dummy" pills reported loss of symptoms compared with those receiving no treatment at all. Rates of improvement also doubled in the placebo group, an effect usually only associated with powerful IBS medications.
Study leader Dr Ted Kaptchuk, from Harvard Medical School in Boston, said: "Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had 'placebo' printed on the bottle.
"These findings suggest that rather than mere positive thinking, there may be significant benefit to the very performance of medical ritual. Placebo may work even if patients know it is a placebo."