OBJECTIVE: Interstitial laser photocoagulation (ILP) is a recently proposed therapeutic procedure for the ablation of benign thyroid nodules, which has already proven to be safe and effective. However, results supporting the routine use of ILP are still limited. DESIGN: The aim of the study was to evaluate the efficacy and safety of ILP treatment in benign nonfunctioning thyroid nodules and to establish whether the therapeutic outcome may be predicted by any clinical parameter at baseline. Twenty-three patients with either a solitary nodule or a dominant nodule within a multinodular goiter underwent ILP and were evaluated 1 and 3 months later. In order to assess the efficacy of low-energy ILP, the procedure was performed with an output power of 3 W, delivering a mean energy of 33.4 +/- 12.7 Joule/mL of nodule volume, which is much lower than previously reported. MAIN OUTCOME: Nodule volume significantly decreased after ILP as assessed after 1 and 3 months (analysis of variance; F = 5.37; p = 0.007). Patients with multinodular goiter showed a greater reduction at 3 months compared with patients bearing a solitary thyroid nodule (38.6 +/- 5.3 vs. 30.9 +/- 6.5%; p < 0.01). Age, sex, ultrasound pattern (isoechogenous/hypoechogenous), pretreatment volume, number of ILP treatments, and total energy delivered did not show any significant correlation with treatment outcome. CONCLUSIONS: Our results demonstrate that ILP can produce a significant reduction of thyroid nodule volume even when a much lower energy than previously reported is delivered. ILP constitutes a minimally invasive technique, which can be carried out on an outpatient basis and could represent a valid nonsurgical alternative for thyroid nodule management. Dominant nodules within a multinodular goiter appear to be more responsive to ILP compared with solitary thyroid nodules.