Few studies have assessed the temporal association between homelessness and injection drug use, and injection-related risk behavior. <i>Methods</i> Among a cohort of 1405 current and former injection drug users in follow-up from 2005 to 2009, we used random intercept models to assess the temporal association between homelessness and subsequent injection drug use, and to determine whether the association between homelessness and sustained injection drug use among active injectors differed from the association between homelessness and relapse among those who stopped injecting. We also assessed the association between homelessness and subsequent injection-related risk behavior among participants who injected drugs consecutively across two visits. Homelessness was categorized by duration: none, <1 month, and ≥1 month. <i>Results</i> Homelessness was reported on at least one occasion by 532 (38%) participants. The relationship between homelessness and subsequent injection drug use was different for active injectors and those who stopped injecting. Among those who stopped injecting, homelessness was associated with relapse [<1 month: AOR = 1.67, 95% CI (1.01, 2.74); ≥1 month: AOR = 1.34 95% CI (0.77, 2.33)]. Among active injectors, homelessness was not associated with sustained injection drug use [<1 month: AOR = 1.03, 95% CI (0.71, 1.49); ≥1 month: AOR = 0.81 95% CI (0.56, 1.17)]. Among those injecting drugs across two consecutive visits, homelessness ≥1 month was associated with subsequent injection-related risk behavior [AOR = 1.61, 95% CI (1.06, 2.45)]. <i>Conclusion</i> Homelessness appears to be associated with relapse and injection-related risk behavior. Strengthening policies and interventions that prevent homelessness may reduce injection drug use and injection-related risk behaviors.