Subcutaneous injections consisting of the detergent, sodium deoxycholate, alone or in combination with the phospholipid, phosphatidylcholine, have been reported to reduce adipose tissue. The role of phosphatidylcholine remains unclear. To evaluate the safety profile and efficacy of subcutaneously injected deoxycholate alone compared with a conventionally utilized mixture of phosphatidylcholine/deoxycholate in patients with undesirable accumulations of submental fat. This was a single center, randomized, double-blind exploratory study. A total of 42 subjects were enrolled; 28 were injected into the submental fat with 1 mL of deoxycholate or phosphatidylcholine/deoxycholate, and 14 received 2 mL per treatment. Subjects received up to 5 treatments every four weeks, and completed a home diary and post-treatment self-assessment. Clinicians blinded to treatment performed injections, physical examination, and photographic evaluation. Photographic assessment of 32 of the 42 enrolled patients revealed modest changes in submental profiles after a median of 5 deoxycholate or 4 phosphatidylcholine/deoxycholate treatments. Mean degree of improvement (0=none, 1=mild, 2=moderate, 3=significant) was 0.8 (+/-0.9) for deoxycholate and 0.6 (+/-0.5) for phosphatidylcholine/deoxycholate, with a median improvement of 0.5 (range, 0-3) for both groups. The incidence of correct before:after photographic sequence assignments was similar. There were no notable differences on physical examination, incidence, duration, and severity of adverse events (most commonly edema, erythema, pain, and burning) or subject self-assessment of fat loss, skin tightening, chin profile, and overall performance between the treatments. Under the conditions employed, injections of deoxycholate or phosphatidylcholine/deoxycholate into the submental fat produced minimal aesthetic improvement overall. No apparent differences in efficacy or adverse events were observed with the inclusion of phosphatidylcholine. Enhanced neck profiles in several subjects demonstrate a proof of concept that warrants further study utilizing a validated, submental profile grading scale and methods to optimize dose and technique.