Purpose: Anal fistula is a common condition in proctology, usually requiring surgical treatment. Few risk factors have been clearly identified based on solid evidence. Our research objective was to determine whether history of anal surgery was a risk factor for subsequent anal fistula. Methods: We conducted a case-control study from January 1, 2012 through December 31, 2013 in our tertiary center, comprising 280 cases that underwent surgery for anal fistula and 123 control patients seeking a consultation for upper gastrointestinal symptoms. Patients with inflammatory bowel disease were excluded. For both cases and controls, the following variables were recorded: sex, any prior anal surgery, diabetes mellitus, infection with human immunodeficiency virus, and smoking status. For each variable, confidence interval and odds ratio (OR) were calculated. Results: In univariate analysis, male sex (73.2% vs. 31.7%, P < 0.0001), active smoking (38.1% vs. 22%, P = 0.0015), and prior anal surgery (16.0% vs. 4.1%, P = 0.0008) were associated with higher risk of anal fistula. In multivariate analysis, only male sex (OR, 5.5; 95% confidence interval [CI], 5.42 to 9.10; P < 0.0001) and previous anal surgery (OR, 4.48; 95% CI, 1.79 to 13.7; P = 0.0008) remained independently associated with anal fistula occurrence. Conclusion The epidemiology of anal fistula is poorly assessed despite the high frequency at which it is diagnosed. Our findings suggest that history of any kind of anal surgery is a risk factor for further onset of anal fistula. Surgeons and patients must be informed of this issue.