Transgender women are disproportionately impacted by HIV infection. We report herein the findings of a pre-post evaluation of the TransLife Care (TLC) project in Chicago, Illinois, on behaviors associated with HIV transmission among transgender women. Participants who received any TLC component versus those who did not were compared using mixed-effects logistic regression with random intercepts across follow-up time points. Ninety-seven participants aged 18 to 59 (median age 24) enrolled; 76.3% were transgender women of color. There was a decrease in condomless sex without consistent PrEP use at 8 months, which was not significantly different between those who did and did not receive the TLC intervention, controlling for calendar time. Evidence does not indicate that the TLC reduces condomless sex without PrEP protection among urban transgender women. However, given the preponderance of evidence of the influence of structural barriers on condomless sex, future research should continue to test the efficacy of structural interventions.