Calcium hydroxylapatite microspheres in a carrier gel (CaHA; Radiesse®: Merz North America, Inc., Raleigh, NC) is approved by the United States Food and Drug Administration for subdermal implantation for the correction of moderate-to-severe facial wrinkles and folds, such as nasolabial folds (NLFs). Lidocaine is often mixed with injectable dermal fillers to reduce injection pain. A new formulation of CaHA has been developed with the convenience of integral 0.3% lidocaine, CaHA (+).<br /> This multicenter, split-face, double-blind study randomized subjects to receive treatment with CaHA (+) in one NLF and CaHA without lidocaine in the contralateral NLF. The pain level for each NLF was evaluated immediately following the injection using a 10-cm visual analog scale (VAS), and every 15 minutes for 60 minutes plus follow-up visits. Additional endpoints included aesthetic outcomes and subject preference. All subjects (N=102) received treatment.<br /> CaHA (+) treatment resulted in a statistically and clinically significant reduction in pain ratings immediately after injection compared with CaHA. The mean difference in VAS scores for pain was -4.41 (<em>P</em><0.0001). In 90% of subjects, the VAS scores were ≥2.0 cm lower for the CaHA (+)-treated NLF. A significant reduction in pain ratings throughout the first hour after injection was observed with CaHA (+) compared with CaHA (<em>P</em><0.0001). Both treatment groups achieved significant aesthetic improvement; however, the pain differential resulted in a subject-reported preference for CaHA (+). CaHA (+) with integral lidocaine significantly reduces pain and is as effective as CaHA.<br /><br /> <em>J Drugs Dermatol</em>. 2016;15(8):1005-1010.