Associations between past use of alcohol, cannabis, and cocaine and various domains of schizotypy were examined in first-degree relatives of patients with schizophrenia and non-psychiatric controls. Substance use was operationalized in three ways: (1) having ever used the substance, (2) age at first use, and (3) past frequency/amount of use during three time periods in late adolescence/early adulthood. Schizotypy was assessed using the Schizotypal Personality Questionnaire (SPQ). Participants who had ever used cannabis had significantly higher cognitive-perceptual, interpersonal, and total schizotypy scores compared to those who had not. Younger age of alcohol use onset was associated with more schizotypy in adulthood, and younger age of first cannabis use was related to more interpersonal schizotypy. More frequent/heavier use of alcohol in the 25-29 age-range, and cannabis in early adulthood, were associated with more schizotypy. The use of addictive substances, particularly cannabis, is related to schizotypy in complex ways.