OBJECTIVES: Biosimilars are biotherapeutic products that are similar in terms of quality, safety and efficacy to an already licensed reference biologic. There are strict guidelines in place for the regulatory approval of biosimilars. However, HTA agencies differ in their approaches to appraisal of biosimilars. This study examined the factors influencing regulatory and reimbursement decisions for biosimilars in different countries. METHODS: A qualitative documentary analysis was performed of the regulatory approval and reimbursement of four biosimilars in nine countries. Regulatory and HTA documents were analyzed to identify the processes of appraisal, indications assessed and key factors driving agency decisions. RESULTS: Overall, twenty-one indications were appraised for the four biosimilars collectively; 90% of appraisals produced a decision of ‘recommended’, 9% were ‘recommended with restrictions’, and 1% were ‘not recommended’. Demonstration of clinical comparability between the biosimilar and the reference product was a requirement in all countries. Cost-minimization and budget impact analyses were key economic decision factors. Some agencies accepted the notion of comparability for extrapolation to indications other than those that had been studied in clinical trials. Pricing dynamics were seen to differ between biosimilars, driven by a combination of pricing strategies for reference biologics, and payer and physician reservations about potential risks. CONCLUSIONS: Regulatory bodies follow common principles of assessment but differences exist with respect to scope and choice of reference product. Important factors common to reimbursement agencies included comparable efficacy and safety of biosimilars to the reference products, and economic considerations; however, they differed in their appraisal processes. The relative weight of price versus potential risk may vary with the disease area targeted by the biologic. The currently approved biosimilars have been relatively simple biologics to re-create and therefore evaluate, but the experience gained should be built upon to address the challenges of assessing the increasingly complex biosimilars being developed.