Little is known about motivation for treatment and readiness for change during an acute medical event. We present data from a cohort of 353 actively substance abusing adults assessed at baseline and every three days during their hospital admission for readiness to change substance use behaviors (URICA), self-reported motivations for substance abuse treatment, and pain and withdrawal symptoms. Factors independently associated with being in a higher (i.e., contemplation or action) stage of change included female sex (AOR=2.33; 95% CI: 1.42, 3.81), being on probation or parole (AOR=2.55; 95% CI: 1.32, 4.93), bipolar disorder (AOR 2.60; 95% CI: 1.20, 5.63), believing they would get sick again if drug use continued (AOR=2.24; 95% CI: 1.36, 3.70), being "tired of using" (AOR=2.91; 95% CI: 1.21, 6.96) and family concerns (AOR=1.78; 95% CI: 1.08, 2.96). During their hospitalization 43.6% increased from precontemplation or contemplation to a higher stage or remained in the action stage. Believing one would get sick again if substance use continued (AOR=2.42; 95% CI: 1.07, 5.48), physical health concerns (AOR=5.28; 95% CI: 1.36, 20.44) and citing "tired of using" as a primary motivator (AOR=2.88; 95% CI: 1.10, 7.54) were independently associated with increased stage of change.