We conducted a 54-week, multicenter, placebo-controlled study from August 2000 to October 2002 at 32 centers located in the United States and Canada. Following a 2-week, single-blind, placebo lead-in period, participants entered a 52-week, double-blind treatment period in which they were randomized at a 2 to 1 ratio to receive 120 mg of orlistat or placebo 3 times daily (Figure 1). Placebo and orlistat capsules looked identical and, except for the active ingredient, had exactly the same composition. General guidelines for diet, exercise, and behavioral modification were supplied to all centers involved in the study (as detailed below), but each center remained free to use its own strategy. There was no study-specific assessment of the compliance with these general guidelines.