Background: Cellulite of the upper lateral and posterior thighs and lower buttocks represents a common, physiological and unwanted condition whose etiologies and effective management are subjects of continued debate. Objective: The purpose of this controlled, double‐blinded study is to evaluate the efficacy and safety of a novel phosphatidylcholine‐based, cosmeceutical anti‐cellulite gel combined with a light‐emitting diode (LED) array at the wavelengths of red (660 nm) and near‐infrared (950 nm), designed to counter the possible mechanisms that purportedly accentuate the presence of thigh cellulite. Methods: Nine healthy female volunteers with Grade II–III thigh cellulite were randomly treated twice daily with an active gel on one thigh and a placebo gel on the control thigh for 3 months. Twice weekly, each thigh was exposed for a 15‐minute treatment with LED light for a total of 24 treatments. At 0, 6, and 12 weeks of the study the following clinical determinants were obtained: standardized digital photography, height and weight measurements, standardized thigh circumference tape measurements, pinch testing, body mass index (kg/m2), body fat analysis (Futrex‐5500/XL near‐infrared analyzer), and digital high‐resolution ultrasound imaging of the dermal–adiposal border. In selected patients, full‐thickness biopsies of the placebo and active‐treated sites were obtained. At 18 months, repeat standardized digital photography, height and weight measurements, and body mass index measurements were obtained. Results: At the end of 3 months, eight of nine thighs treated with the phosphatidylcholine‐based, anti‐cellulite gel and LED treatments were downgraded to a lower cellulite grade by clinical examination, digital photography, and pinch test assessment. Digital ultrasound at the dermal‐adiposal interface demonstrated not only a statistically significant reduction of immediate hypodermal depth, but also less echo‐like intrusions into the dermal layer. Three of six biopsies from thighs treated for 3 months with the active gel and LED treatments demonstrated less intrusion of subcutaneous fat into the papillary and reticular dermis. In nine placebo and LED‐treated thighs and one of the actively treated thighs, minimal clinical changes were observed or measured by the clinical determinants throughout the 3‐month study. At the month‐18 evaluation period for the eight responsive thighs, five thighs reverted back to their original cellulite grading, while three thighs continued to maintain their improved status. Patients experienced minimal and transient side effects that included puritus, erythema and swelling. Conclusions: The results of this small but well‐documented, randomized, double‐blinded study affirms that eight of nine thighs with Grade II–III cellulite responded positively to a novel, combined 3‐month treatment program of a phosphatidylcholine‐based, anti‐cellulite gel and LED exposure, as determined by the clinical determinants obtained. Patients experienced minimal and transient side effects. At the month‐18 evaluation period (15 months after treatment), five responsive thighs reverted back to their original cellulite grading, indicating a need for maintenance treatment. Future studies are needed to verify these tentative positive observations.