Perianal Crohn's disease (pCD) represents an aggressive phenotype with limited studies on long-term outcomes. We evaluated 5-year outcomes of these patients on biologic therapies. We performed a retrospective analysis of patients with pCD at a tertiary medical center. We used Kaplan-Meier curves to estimate rates and multivariate logistic regression to identify predictors of long-term outcomes. We included 311 patients with pCD of which 168 patients were started on biologics [138 anti-tumor necrosis factor (TNF) α, 14 vedolizumab, 16 ustekinumab] at the time of diagnosis. Anti-TNF use at the time of diagnosis was associated with decreased rates of perianal abscess recurrence [hazard ratio (HR)=0.48, 95% confidence interval (CI): 0.32-0.74], whereas ustekinumab use was associated with increased rates of perianal fistula closure (HR=3.58, 95% CI: 1.04-12.35) and decreased rates of perianal abscess recurrence (HR=0.20, 95% CI: 0.07-0.56) at follow-up. Among patients who failed their first anti-TNF, switching to another anti-TNF was associated with decreased rates of colectomy (HR=0.20, 95% CI: 0.04-0.90) and permanent diversion (HR=0.16, 95% CI: 0.03-0.94) compared with ustekinumab, whereas vedolizumab use was associated with decreased perianal fistula closure (HR=0.22, 95% CI: 0.05-0.96) compared with ustekinumab. Predictors of colectomy included colonic disease (odds ratio=2.71, 95% CI: 1.36-5.38) and anal stenosis (odds ratio=4.44, 95% CI: 1.59-12.43). Type of biologic use at the time of pCD diagnosis or after first anti-TNF failure may be associated with long-term outcomes in patients with pCD.