A phase 4, open-label, multicenter, community-based study was conducted in subjects with mild to moderately severe papulopustular rosacea of various etiologies and locations to identify subgroups particularly responsive to twice-daily application of metronidazole topical gel 0.75% to the affected areas of the face. A total of 582 subjects were randomized. Evaluations were conducted at baseline and at weeks 4, 8, and 12. At each evaluation, investigator global assessment (IGA) scores, mean papule and pustule counts, erythema scores, and telangiectasia scores improved significantly (P < .0001), with consistent results across sex and age subgroups. The mean erythema severity score decreased significantly (P < .0001) from baseline by week 4 and continued to decline at all study visits, with a nearly 50% reduction by week 12. At study end, subjects indicated a 25% improvement in itching, pain, soreness, or stinging; a 53% improvement in embarrassment or self-consciousness; and a 31% improvement in rosacea's effect on social or leisure activities. Metronidazole topical gel 0.75% was associated with a very low incidence of side effects in this trial, similar to previous clinical trials. The most common treatment-related adverse event (AE) reported in this study was mild application-site discomfort. The gel formulation was well-tolerated and effective in all subject subgroups and in a variety of climates. The findings of this study expand the collected data on the efficacy and safety of metronidazole topical gel 0.75% beyond that demonstrated in controlled clinical trials and confirm the utility of this therapy in the community setting.