(1) Background: Since its introduction in the 1990s, laparoscopic appendectomy has become established over the years and is today considered the standard therapy for acute appendicitis. In some cases, however, a conversion to the open approach is still necessary. The primary aim of this study was to identify risk factors for the need to convert from the laparoscopic to an open approach during appendectomy for acute appendicitis. (2) Methods: A retrospective analysis of 1220 adult patients who underwent laparoscopic appendectomy for acute appendicitis from 2010 to 2020 at the University Hospital Erlangen was performed. Data, including patient demographics and pre-, intra-, and postoperative findings, were collected and compared between patients with and without conversion. (3) Results: The conversion rate in our cohort was 5.5%. A higher preoperative WBC count and CRP (OR 1.9,p= 0.042, and OR 2.3,p= 0.019, respectively), as well as the presence of intraoperative perforation, necrosis or gangrene, perityphlitic abscess and peritonitis (OR 3.2,p= 0.001; OR 2.3,p= 0.023; OR 2.6,p= 0.006 and OR 2.0,p= 0.025, respectively) were identified as independent risk factors for conversion from the laparoscopic to the open approach. Conversion was again independently associated with higher morbidity (OR 2.2,p= 0.043). (4) Conclusion: The laparoscopic approach is feasible and safe in the majority of patients with acute appendicitis. Only increased inflammatory blood markers could be detected as the preoperative risk factors potentially influencing the choice of surgical approach but only with low specificity and sensitivity. For the decision to convert, intraoperative findings are additionally crucial. However, patients with conversion should receive special attention in the postoperative course, as these have an increased risk of developing complications.