BACKGROUND Ultrasonography-guided alcohol injection (USGAI) of Morton's neuroma represents an alternative to operative treatment. Nonetheless, the literature only reports few small studies evaluating the effectiveness of the treatment. The aim of the present retrospective study was to assess the effectiveness of USGAI to treat Morton's neuroma in 508 patients at 2 medical centers. METHODS Between January 2001 and January 2012, 508 patients with 540 Morton's neuroma had USGAI for Morton's neuroma. Only second and third web-space neuromas were included in this study. RESULTS A mean number of 3.0 (range, 1 to 4) injections were performed for each neuroma. Mean local inflammatory reaction was 0.7 (range, 0 to 2). There were no other local or systemic complications. The overall mean pre-USGAI VAS score was 8.7 (range, 6 to 10), while the post-USGAI VAS score at 1 year was 3.6 (range, 0 to 9). The delta VAS between the pre- and post-USGAI was statistically significant (P < .0001). At 1-year follow-up 74.5% of patients were satisfied with the procedure. CONCLUSIONS USGAI produced encouraging results in over 500 patients affected by Morton's neuroma. The procedure proved to be safe in all patients. METHODS Level IV, retrospective case series.