Injectable calcium hydroxylapatite is a soft-tissue augmentation material that is used off-label for facial augmentation, including repletion of depressed nasolabial folds. We sought to assess the safety of calcium hydroxylapatite injection for correction of nasolabial fold depressions. Specifically, we sought to obtain a quantitative assessment of injection-related adverse events using a reproducible placement technique with long-term follow-up. We conducted an open-label, single-center prospective study using reproducible technique with 1- to 1.5-year follow-up. All patients were treated with infraorbital nerve blocks. Then, parallel linear threading technique using 27-gauge/1.25-in needles was used to place 1 to 2 mL of injectant at the dermal subcutaneous junction into each pair of depressed folds. A triangular array of injectant was deposited under the melonasal junction. At follow-up at 2 to 3 weeks and at 1 to 1.5 years, respectively, patients were asked to report and characterize injection-related redness, swelling, bruising, nodule or granuloma formation, asymmetric correction, textural change, hypersensitivity reactions, degree of correction remaining, and overall satisfaction. In addition, patients who had received other injectable soft-tissue materials were asked to compare these with calcium hydroxylapatite in terms of risk profile and longevity of effect. In all, 22 patients were treated and complete follow-up data were obtained from 18. Of the 18 patients, all reported at least mild postinjection redness and swelling, which abated within 1 to 5 days. Bruising was reported by fewer than half, and resolved within 4 to 10 days. Palpable but not visible nodules were reported by 2 of 18 patients; these resolved within 3 months of injection. Asymmetric correction, textural change, granulomas, and hypersensitivity reactions were not reported. In all, 14 of 18 patients reported that cosmetically significant correction lasted longer than 1 year. Two thirds of injected patients who had received other fillers for nasolabial fold correction preferred calcium hydroxylapatite, with the primary reason being increased longevity of effect. There was a lack of objective outcomes measures. When a consistent, defined injection technique is used, injectable calcium hydroxylapatite appears to be a well-tolerated soft-tissue augmentation material for correction of nasolabial fold depressions. A long duration of effect may make this material particularly desirable for some patients.