To determine whether particular environmental, medical, or behavioral risk factors existed among Cryptcoccus gattii-infected persons compared with the general population, we conducted a sex-matched case-control study on a subset of case-patients in British Columbia (1999-2001). Exposures and underlying medical conditions among all case-patients (1999-2007) were also compared with results of provincial population-based surveys and studies. In case-control analyses, oral steroids (matched odds ratio [MOR] 8.11, 95% confidence interval [CI] 1.74-37.80), pneumonia (MOR 2.71, 95% CI 1.05-6.98), and other lung conditions (MOR 3.21, 95% CI 1.08-9.52) were associated with infection. In population comparisons, case-patients were more likely to be ≥50 years of age (p<0.001), current smokers (p<0.001), infected with HIV (p<0.001), or have a history of invasive cancer (p<0.001). Although C. gattii is commonly believed to infect persons with apparently healthy immune systems, several immunosuppressive and pulmonary conditions seem to be risk factors.