Flat warts are a common and recurrent skin disease that has no specific antiviral treatment. As an alternative or complementary therapy, fire needle therapy has been widely used in the treatment of flat warts. The objective of this study was to systematically evaluate the efficacy and safety of fire needle therapy for flat warts. Using the search terms “flat warts” and “fire needle,” we searched the PubMed, Embase, Cochrane, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Chinese biomedical (SinoMed) database, and the China Science and Technology Journal databases for studies until March 12, 2020. Randomized controlled trials comparing fire needle therapies with conventional therapies were also included. We calculated the risk ratios (RR) and mean differences with a 95% confidence interval (CI). We analyzed 29 trials involving 2,666 patients. Results showed that the use of fire needle therapy alone may have a higher efficacy rate compared with that of an immunomodulator (RR = 1.11, 95% CI: 1.03 to 1.20, I2 = 0%,
P
= 0.006; RR = 1.19, 95% CI: 1.03 to 1.37, I2 = 70%,
P
= 0.02, respectively) or tretinoin (RR = 1.39, 95% CI: 1.25 to 1.55, I2 = 0%,
P
< 0.00001), with a lower risk of blisters (
P
= 0.03) or erythema (
P
= 0.04), but with a higher risk of pigmentation (
P
= 0.02). We also determined the efficacy rate of fire needle therapy in combination with traditional Chinese medicine (RR = 1.16, 95% CI: 1.10 to 1.23, I2 = 21%,
P
< 0.00001), immunomodulators (RR = 1.17, 95% CI: 1.07 to 1.28, I2 = 33%,
P
= 0.0005), imiquimod (RR = 1.21, 95% CI: 1.04 to 1.42,
P
= 0.02), or as multidrug therapies (RR = 1.15, 95% CI: 1.07 to 1.24, I2 = 0%,
P
= 0.0001) and found that the combination treatments could reduce recurrence rates (
P
< 0.00001) and provided a lower risk of desquamation (
P
= 0.006). In conclusion, fire needle therapy seems to be effective for flat warts, with a reduced incidence of adverse events, such as blisters, erythema, and desquamation, but may increase incidence of pigmentation.