OBJECTIVES: NICE in the UK has a remit to compare new interventions to established care, which could include off-label medication. The objective was to update the assessment of how frequently NICE request off-label comparators and the subsequent implications. METHODS: All NICE single technology appraisal (STA) scopes from 01/01/08 to 18/12/13 were reviewed. Off-label comparators were identified as those that were being used outside their licence according to the Electronic Medicines Compendium. In cases where off-label comparators were requested in the scope, the manufacturer’s submission, the Evidence Review Group report and the final NICE guidance were reviewed to ascertain the outcome of this request. RESULTS: Of 111 completed STAs reviewed, the scopes of 31 (27.9%) requested comparison to at least one off-label comparator; the proportion has been relatively stable over time. Since the previous analysis at the end of 2012, there has been a slight shift to more manufacturers not comparing to the requested off-label comparator (51.6% at end 2013 versus 45.8% at end 2012; driven by 80% of 2013 cases). NICE accepted the decision to not compare to the off-label agent in a much higher proportion of appraisals at the end of 2013 (81.3%) versus at the end of 2012 (63.6%). Two appraisals where NICE had originally rejected the new technology in favour of an off-label comparator had been re-appraised and NICE reversed their decision and now recommend the new interventions (TA274 and TA301). Overall however, NICE have rejected 8 new interventions (25.8% of scopes with off-label comparators requested) between 2008 and 2013 for not being cost-effective, thereby indirectly recommending the off-label alternative. CONCLUSIONS: NICE have rejected new interventions in favour of off-label comparators. However, there may be a recent shift towards more manufacturers choosing not to compare to the requested off-label comparator and for NICE to accept this decision.