Objective: To compare and contrast adverse drug reaction (ADR) reporting between 2 psychiatric hospitals, as well as preventability and possible reasons that one hospital had more preventable occurrences than the other. Methods: A 3-year retrospective analysis was conducted comparing ADRs previously reported in a study from Maryland Psychiatric Hospital that were classified as probable and definite according to the modified Naranjo probability scale versus probable and definite ADR reports from the Colorado Mental Health Institute at Pueblo (CMHIP). The same study period (July 1, 2006–June 30, 2009) was used for the retrospective analysis of ADRs at both institutions. We compared the most frequently reported classes of medications and examined the number of reactions, types of reactions, and preventability. Results: Psychiatric medications were responsible for 98/145 (67.6%) ADRs at CMHIP, while 47 (32.4%) ADRs were caused by nonpsychiatric medications. At Maryland Psychiatric Hospital, 48.4% of ADRs were caused by psychiatric medications and 51.6% were caused by nonpsychiatric medications. Of the 145 ADRs reported at CMHIP, only 1 (0.7%) was classified as preventable, versus 19 (20.4%) preventable ADRs reported in Maryland Psychiatric Hospital. The classes of medications most frequently associated with ADRs at Maryland Psychiatric Hospital were cardiovascular agents, antiepileptic drugs, and second-generation antipsychotic medications; at CMHIP the medications most commonly associated with ADRs were second-generation antipsychotics, conventional antipsychotics, and mood stabilizers. Proposed reasons for differences in numbers, types, and preventability of ADRs between the institutions are that different reporting mechanisms and pharmacy medication monitoring programs, in conjunction with quality assurance programs, were used at the 2 institutions. Conclusions: Differences between 2 comparable hospitals in the number and preventability of ADRs and the classes of medications reportedly responsible for them may be due to different reporting mechanisms and monitoring programs. Pharmacy intervention programs may lead to prevention of ADRs.