"Ai-Mai-Mi Surgical Friends" is a comedic anime and manga series that blends absurd humor with surreal storytelling. The narrative revolves around three high school girls—Ai, Mai, and Mi—who are members of their school's manga club. Despite their shared interest in manga, their personalities and approaches to life are wildly different, leading to chaotic and often nonsensical interactions. Ai is the most level-headed of the trio, often serving as the voice of reason, though she is not immune to the group's eccentricities. Mai is energetic and impulsive, frequently driving the group into bizarre situations, while Mi is quiet and reserved, often providing deadpan reactions to the absurdity around her.

The series lacks a conventional plot structure, instead presenting a series of loosely connected vignettes that highlight the girls' daily lives and their misadventures in the manga club. These episodes often involve surreal and exaggerated scenarios, such as the girls encountering supernatural phenomena, engaging in absurd competitions, or breaking the fourth wall to comment on their own story. The humor is heavily reliant on slapstick, wordplay, and meta-commentary, with frequent references to otaku culture and manga tropes.

The manga club itself serves as a backdrop for much of the humor, with the girls attempting to create their own manga while dealing with their lack of talent and motivation. Their interactions with other characters, such as their eccentric teacher and rival club members, further amplify the comedic tone. Despite the lack of a overarching narrative, the series maintains a consistent focus on the dynamics between Ai, Mai, and Mi, emphasizing their friendship and the absurdity of their shared experiences.

The anime adaptation retains the manga's chaotic energy, with fast-paced animation and exaggerated visual gags that complement the source material's humor. Both the manga and anime are characterized by their self-aware tone and willingness to embrace absurdity, making them a unique entry in the comedy genre. The series does not aim for deep character development or emotional depth, instead prioritizing humor and entertainment through its unpredictable and often nonsensical storytelling.