Situs inversus (SI) and midgut malrotation (MM) are uncommon anatomic anomalies that complicate diagnosis and management of acute abdominal pain. We present two cases of left-sided acute appendicitis with situs inversus totalis and a literature review of studies published in English language on left-sided acute appendicitis, accessed via Pubmed and Google Scholar database. Sixty-three published cases of left-sided acute appendicitis were evaluated, and two patients (M:16 yr, F:17 yr) who presented to our clinic with left lower quadrant pain caused by left-sided acute appendicitis were reported. Thirty-five of the patients were male and 30 were female (including our patients) with age range from 8 to 63 years and median age of 26.7 +/- 14.0 years. Fifty-three patients had situs inversus totalis (SIT), 8 had MM and two were with malrotation of the caecum. Thirty-eight patients had applied to the hospital with left lower quadrant pain, 12 with right and 6 with bilateral lower quadrant pain. Thirty patients were diagnosed as having SIT or MM, while the diagnosis in 12 patients was established during the intraoperative period. Eleven patients with SIT were aware of having this anomaly. Five of the patients underwent laparoscopic appendectomy and in two patients laparoscopic appendectomy and cholecystectomy were performed in one session. Preoperative diagnosis has been easier to achieve after 1985, when ultrasonography (USG) and computed tomography (CT) were introduced into the medical practice. SIT and MM should be taken into consideration in patients with findings of the physical examination suspicious for left-sided acute appendicitis. X-ray, USG, CT and diagnostic laparoscopy are beneficial in developing the differential diagnosis.