Data on the association between peripheral artery occlusive disease (PAOD) and leptospirosis are limited. We conducted a retrospective cohort study for determining whether leptospirosis is one of the possible risk factors for PAOD. Patients diagnosed with leptospirosis by using 2000 to 2010 data from the Taiwan National Health Insurance Research Database. Patients with leptospirosis without a history of PAOD were selected. For each leptospirosis patient, 4 controls without a history of leptospirosis and PAOD were randomly selected and frequency-matched for sex, age, the year of the index date, and comorbidity diseases. The follow-up period was from the time of the initial diagnosis of leptospirosis to the diagnosis date of PAOD, or December 31, 2011. The Cox proportional hazard regression models were used for analyzing the risk of PAOD. During the follow-up period, the cumulative incidence of PAOD was higher among the patients from the leptospirosis cohort than among the nonleptospirosis cohort (log-rank test, P < 0.001). In total, 29 patients with PAOD from the leptospirosis cohort and 81 from the nonleptospirosis cohort were observed with the incidence rates of 2.1 and 1.3 per 1000 person-years, respectively, yielding a crude hazards ratio (HR) of 1.62 (95% confidence interval [CI] = 1.44-1.81) and adjusted HR (aHR) of 1.75 (95% CI = 1.58-1.95).The risk of PAOD was 1.75-fold higher in the patients with leptospirosis than in the general population.