Background: Suicide is a major public health concern, particularly among people who use illicit substances and/or non-prescribed medications. Methods: The present study prospectively assessed the incidence and predictors of suicidal ideation (SI) and suicide attempt (SA) among 868 substance-using patients over 12 months after receiving primary care within seven public primary care clinics. Results: Participants reported a high incidence of SI (25.9%) and SA (7.1%) over the year following primary care visits. Suicidality was elevated in patients who were female; lacked a high school diploma; were unemployed; reported depression, anxiety, hallucinations, concentration difficulty, or violent behavior; used nicotine or stimulants; used the emergency department or mental health services in the past 90 days; reported current quality-of-life impairment in mobility or usual activities; or reported recent SI or lifetime SA at baseline. In multiple regression analyses, only past 30-day SI, any lifetime SA, past 90-day violent behavior, and current impairment due to anxiety or depression at baseline uniquely predicted SI or SA beyond other variables. Conclusions: Results support the need for screening for suicidality among primary care patients who use illicit substances and identify key of these patients who are at particularly elevated risk for suicidality.