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A new family of next-generation non-animal hyaluronic acid (HA) dermal fillers was approved by the FDA in June 2006. Compared with other HA fillers available in the United States at the time of writing, these new fillers have a higher concentration of HA, higher concentration of cross-linked HA, and a smooth consistency—which should promote long-lasting corrections and a smooth, natural look and feel postinjection.The objective was to compare the effectiveness and safety of these smooth-gel HA dermal fillers with bovine collagen for nasolabial fold (NLF) correction.A total of 439 subjects with moderate or severe NLFs received one of three types of smooth-gel HA dermal filler (in one NLF) and cross-linked bovine collagen (in the other NLF) and were evaluated for ≤24 weeks.All three HA dermal fillers achieved considerably longer-lasting clinical correction than bovine collagen; 81% to 90% of HA dermal filler–treated NLFs maintained a clinically significant improvement from baseline for ≥6 months. Up to 88% of subjects preferred the HA dermal fillers over bovine collagen. All fillers were similarly well tolerated.The smooth-gel HA dermal fillers offer longer-lasting correction than bovine collagen—which may lessen the frequency that repeat treatments are needed. Also, they were preferred by the vast majority of subjects—which should promote patient satisfaction.