Background: Coma blisters are most commonly associated with barbiturate and benzodiazepine overdose; however, they have also been described in association with many other substances, including amitriptyline. Objective: To review the literature on the clinical manifestations of coma blisters in the setting of amitriptyline overdose. Methods: Case report and literature review. Results: Coma blisters in association with amitriptyline overdose have rarely been documented in the literature. Of the few reported cases, peripheral neuropathy has been present two (including our case report) out of four times. Conclusion: Amitriptyline is known to impair endothelial cell tight junction integrity. Thus, individuals with amitriptyline overdose may be predisposed to microvascular damage during the compression imposed from a comatose state. This may help to explain the tendency for patients to present with the interesting triad of coma, blisters, and neuropathy.