Background: We assessed the prevalence of complications from percutaneous ethanol injection (PEI) for benign and cystic thyroid nodules (CTNs) and their management. Methods: We conducted a systematic review with meta-analysis of data from published observational studies on PEI of CTNs. We also included unpublished retrospectively collected data on complications after PEI from all consecutive patients with cytologically benign CTNs who underwent PEI at the Unit of Endocrinology and Metabolic Diseases, AOU University of Campania Luigi Vanvitelli (Naples, Italy) between June 1, 2021, and March 31, 2024. A random effects meta-analysis was performed on the prevalence rate data. Pooled prevalence data were presented with confidence intervals (CIs). The I2 statistic index was used to quantify the heterogeneity. The details of the complications and the management were qualitatively described. Results: The literature search yielded 1189 studies, of which 48 studies were included in the systematic review and meta-analysis, in addition to our institutional experience (3670 CTNs in total). The overall quality of each included study was judged as fair. The prevalence of "Overall" complications of PEI was 32% ([CI 25-40%], I2 92.7%, 967 of 3195 thyroid nodules [TNs]). The prevalence of "Minor" complications of PEI was 32% ([CI 25-40%], I2 92.7%, 952 of 3195 TNs). The prevalence of "Major" complications of PEI was 2% ([CI 1-2%], I2 0%, 22 of 3670 TNs). Sensitivity analyses did not modify the results. The pooled prevalence rate of local pain was 21% (CI [16-27] I2 90.3). Local pain was typically transient and mild, sometimes moderate, and requiring analgesics for few days. The pooled prevalence rate of dysphonia was 1% (CI [1-2], I2 0). Dysphonia was transient and could last from several hours to 12 months after PEI. Conclusions: Complications of PEI for benign and CTNs are relatively common, but most are minor and usually transient, not requiring treatment. Dysphonia was a major complication, but it was uncommon and transient. PEI for CTNs could be considered a generally safe technique.