Painful anal fissures could be distressing conditions that severely impair the patients' quality of life. The analgesic effectiveness of topical drugs, such as calcium-antagonists and nitrates is quite variable. The inhalational anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We report a pioneer experience treating a painful chronic anal fissure with topical sevoflurane. A young adult male was suffering from an extremely painful chronic anal fissure, which severely affected his quality of life. The topical treatment with nitroglycerine and diltiazem gels failed. The patient agreed to the treatement with topical sevoflurane as an off-label medication, and it produced an immediate, intense, and long-lasting analgesic effect. An intense but rapidly transient burning sensation, as well as persistent but well-tolerated flatulence were the only adverse effects. The quality of life was greatly improved, and the cost of the treatment was affordable. Therefore, the off-label use of topical sevoflurane appears to be an effective alternative for the symptomatic treatment of painful anal fissures.