Background: The Magerl transarticular technique and the Harms–Goel C1 lateral mass-C2 isthmic screw technique are the two most commonly used surgical procedures to achieve fusion at C1–C2 level for atlanto-axial instability. Despite recent technological advances with an increased safety, several complications may still occur, including vascular lesions, neurological injuries, pain at the harvested bone graft site, infections, and metallic device failure. Methods: We retrospectively analyzed all patients (n = 42 cases) undergoing a Harms–Goel C1–C2 fixation surgery with polyaxial C1 lateral mass screws and C2 isthmic screws at two different institutions between 2003 and 2012 and report clinical and radiological complications. One patient was lost to follow-up. The mean follow-up of the remaining 41 patients was 18.7 months (range 12–90). A clinically relevant complication was defined as a complication determining the onset of a new neurological deficit or requiring the need for a revision surgery. Results: A total of 14 complications occurred in 10 patients (24.4% of 41 patients). Greater occipital nerve neuralgia was evident in 4 patients (9.8%). All but one completely resolved at the end of the follow-up. Persistent neck pain was reported by 3 patients (7.3%), hypoesthesia by 1 patient (2.4%), and anesthesia in the C2 area on both sides in 1 patient (2.4%). Furthermore, a superficial, a deep, and a combined superficial and deep wound infection occurred in 1 patient each (2.4%). One patient (2.4%) had pain at the iliac bone graft donor site for several weeks with spontaneous resolution. A posterior progressive intestinal herniation through the iliac scar was seen in 1 case (2.4%), which required surgical repair. No vascular damages occurred. Altogether, 5/41 patients (12.2%) had a clinically relevant complication including 4 patients necessitating a revision surgery at the C1–C2 level (9.8%). Conclusions: Atlanto-axial fixation surgery remains a challenging procedure because of the proximity of important neurovascular structures. Nevertheless, on the basis of our current experience, the C1 lateral mass-C2 isthmic screw technique appears to be safe with a low incidence of clinically relevant complications. Postoperative C2 neuralgia, as the most frequent problem, is due to surgical manipulation during preparation of the C1 screw entry point.