Laparoscopic cholecystectomy is a standard treatment for patients with gallstones in the gallbladder. However, multiple risk factors affect the probability of conversion from laparoscopic cholecystectomy to open surgery. A greater understanding of the preoperative factors related to conversion is crucial to improve patient safety. In the present systematic review, we summarized the current knowledge about the main factors associated with conversion. Next, we carried out several meta-analyses to evaluate the impact of independent clinical risk factors on conversion rate. Male gender (OR = 1.907; 95%CI = 1.254–2.901), age > 60 years (OR = 4.324; 95%CI = 3.396–5.506), acute cholecystitis (OR = 5.475; 95%CI = 2.959–10.130), diabetes (OR = 2.576; 95%CI = 1.687–3.934), hypertension (OR = 1.931; 95%CI = 1.018–3.662), heart diseases (OR = 2.947; 95%CI = 1.047–8.296), obesity (OR = 2.228; 95%CI = 1.162–4.271), and previous upper abdominal surgery (OR = 3.301; 95%CI = 1.965–5.543) increased the probability of conversion. Our analysis of clinical factors suggested the presence of different preoperative conditions, which are non-modifiable but could be useful for planning the surgical scenario and improving the post-operatory phase.