BACKGROUND: Cellulite is a common, unwanted condition, which is challenging to treat. OBJECTIVES: The objective of this investigation was to evaluate safety and effectiveness of a long-pulsed 1064 Nd:YAG laser as a method for improvement in cellulite appearance and to evaluate parameter selection. MATERIALS AND METHODS: Twenty-two female subjects with posterior leg cellulite were randomly assigned to treatment of left or right thigh with higher energy treatment with cryogen spray cooling (CSC) (10-mm spot size; 50 J/cm(2); 50-ms pulse duration and CSC settings of 30-ms duration with a 20-ms delay) or lower energy treatment with no CSC (10 mm; 20 J/cm(2); 50 ms). Subjects received three treatments at 4 weeks intervals. Digital photographs and circumference measurements were taken pre-treatment and up to 6 months post-treatment. RESULTS: Nineteen subjects completed three treatments and 16 subjects completed 6-month follow-up. Circumference measurements pre- and post-treatment were not significantly different. Blinded evaluators noted mild improvement in three of seven subjects in high energy group and moderate improvement in two of nine subjects in low energy group. CONCLUSION: Multiple passes with a long-pulsed 1064 Nd:YAG achieved mild or moderate improvement in some subjects as rated by blinded evaluators.