Abstract Introduction Hypothermia improves neurologic recovery compared to normothermia after resuscitation from out-of-hospital ventricular fibrillation, but may or may not be beneficial for patients resuscitated from in-hospital cardiac arrest. Therefore, we evaluated the effect of induced hypothermia in a large cohort of patients with in-hospital cardiac arrest. Methods Retrospective analysis of multi-center prospective cohort of patients with in-hospital cardiac arrest enrolled in an ongoing quality improvement project. Included were adults with a pulseless event in an in-patient hospital ward of a participating institution who achieved restoration of spontaneous circulation between 2000 and 2009. The exposure of interest was induced hypothermia. The primary outcome was survival to discharge. The secondary outcome was neurological status at discharge. Analyses evaluated all eligible patients; those with a shockable rhythm; or those with endotracheal tube inserted after resuscitation; and the effect of no hypothermia versus hypothermia (lowest temperature>32°C but≤34°C) versus overcooled (≤32°C). Associations were assessed using propensity score methods. Results Included were 8316 patients with complete data, of whom 214 (2.6%) had hypothermia induced and 2521 (30%) survived to discharge. Of patients reported to receive hypothermia, only 40% were documented as achieving a temperature between 32°C and 34°C. Adjusted for known potential confounders using propensity score methods, induced hypothermia was associated with an odds ratio of survival of 0.90 (95% confidence interval: 0.65, 1.23; p-value=0.49) compared to no hypothermia. Induced hypothermia was associated with an odds ratio of neurologically-favorable survival of 0.93 (95% confidence interval: 0.65, 1.32; p-value=0.68) compared to no hypothermia. For patients with shockable first-recorded rhythm, induced hypothermia was associated with an odds ratio of survival of 1.43 (95% confidence interval: 0.68, 3.01; p-value=0.35) compared to no hypothermia. Conclusion Hypothermia is induced infrequently in patients resuscitated from in-hospital cardiac arrest with only 40% achieving target temperatures. Induced hypothermia was not associated with improved or worsened survival or neurologically-favorable survival. The lack of benefit in this population may reflect lack of effect, inefficient application of the intervention, or residual confounding. High-quality controlled studies are required to better characterize the effect of induced hypothermia in this population.