Background/Aims: The International Serious Adverse Events Consortium (iSAEC) is a pharmaceutical industry and FDA-led consortium focused on identifying DNA variants useful for predicting risk of drug-induced rare serious adverse events (SAEs). We assessed the feasibility of using electronic medical databases at six HMORN sites to identify provisional cases of three SAEs: drug-induced liver injury (DILI), serious skin rashes (SSR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and angioedema, and extreme weight gain (EWG) among adults on atypical antipsychotics. Methods: Project work was divided among three teams. HealthPartners and Marshfield Clinic led the DILI team, Kaiser Permanente Hawaii and Kaiser Permanente Georgia led the SSR team and Group Health and Geisinger guided the EWG study. Teams met routinely via biweekly conference calls to coordinate their study efforts; monthly conference calls were conducted to coordinate the overall project, mark progress and discuss challenges and solutions. For each study, standardized case identification criteria were developed with input from iSAEC, expert panels, and medical literature. Potential cases were identified through electronic data searches using diagnoses, medication histories, laboratory test results, and other clinical data elements indicative of DILI and SSR during 2000-2009, or EWG from 2004-2009. Potential cases of DILI and SSR were abstracted to assess provisional case status and determine implicated drugs. Weight trajectories of suspected EWG cases were visually inspected to confirm EWG during atypical antipsychotic treatment period. Results: A total of 99 provisional cases of DILI, 41 cases of SJS/TEN and 56 provisional cases of angioedema were identified from the electronic records of the participating HMOs. For EWG, 249 cases were confirmed and an additional 341 were categorized as "possible" cases, with additional chart review and patient interview required for confirmation. Confirmation rates varied from 17% for DILI to 2-79% for SSR and 23-30% for EWG. Conclusions: The SAEC and HMORN study sites identified well-phenotyped cases with the targeted drug-induced SAEs of interest. The relative success of these efforts has been critical in the planning of a larger second study that will include analyses of genetic factors associated with provisional case SAEs.