The aim of this randomized, double-blind clinical trial was to determine the effectiveness of systemic antibiotic application followed by either topical ionized solution (IS) or topical saline solution (placebo) as surgical site infection (SSI) prophylaxis in appendectomy for non-perforated appendicitis. Prophylactic antibiotic was administered pre-incision and either topical IS or placebo was applied pre-suturing to 529 patients, who were then monitored for 30 days. When topical IS was used, SSI relative risk was 0.739 (95% CI 0.537, 1.019) and the SSI prevention rate was 26.06% (CI -1.8%, 46.3%). The number needed to treat was 14.80 patients and the number needed to harm was 209 in order for SSI to be avoided. In conclusion, there was a trend for topical IS prophylaxis to reduce SSI frequency in patients undergoing appendectomy for non-perforated appendicitis, but the result was not statistically significant.