Pregnancy registries are the most commonly used data resource for the post-marketing surveillance of drug teratogenicity. However, the limited sample size and potential selection bias in these registries has led us to investigate the potential of the UK General Practice Research Database (GPRD) as an alternative data source for monitoring drug safety during pregnancy. In addition, a literature review identified further observational data sources that monitor pregnancy outcomes for future evaluation. Initial feasibility studies focused on the ability of the GPRD to capture pregnancy outcomes for a range of drug class exposures, all of which are currently under investigation in pregnancy registries, during pregnancy. The comparator pregnancy registries were identified via a MEDLINE search, whilst eligible pregnancies, in which women received one or more prescriptions for the drug of interest during pregnancy, were identified in the GPRD using the mother-baby link. The number of pregnancy outcomes following exposure to medication for a range of conditions with varying prevalence, including depression, migraine, epilepsy, herpes simplex and HIV, captured by the two data sources were compared. For depression, a relatively prevalent condition, the GPRD recorded the same number of mean annual intrauterine exposures to fluoxetine as the pregnancy registry (118 exposures/year). Ascertainment of intrauterine exposure to drug treatments for less prevalent conditions was found to be higher for the pregnancy registries than the GPRD; for the older antiepileptic drugs (valproate and carbamazepine), the pregnancy registry recorded between four and five times as many mean annual exposures as the GPRD. Virtually no antiretroviral exposures (three) were identified during the time period of interest on the GPRD, compared with 3946 in the Antiretroviral Pregnancy Registry. Data from the GPRD meet established criteria for evaluating outcomes of pregnancy. For prevalent conditions, it has the potential to replace or work alongside standard pregnancy registries and the alternative data sources identified. Further studies are now needed to assess its ability to replicate known teratogenic associations.