OBJECTIVES Since 2011 Germany follows a formal process of evaluating new pharmaceuticals for their incremental benefit vs. an appropriate comparator to inform price negotiations with Insurers. This study summarizes the rationale underlying the German authorities’ (G-BA) final assessment of manufacturers’ submissions following successful approval by regulators. METHODS G-BA decisions (1/2011 to 2/2014) were evaluated for their alignment (full, partial or none) between manufacturer’s development programs and expectations concerning: (1) target population; (2) comparator; (3) clinical endpoints, including indirect comparisons. Also addressed was the role of safety and how the G-BA addressed the potential for bias.     RESULTS Of 69 completed submissions, 3 were resubmissions and 7 lacked a dossier. 59 completed submissions were subjected to a detailed review. Ten (17%) were for orphan disease indications. Major disagreement existed for 37 (63%), of which 17 (46%) were considered fully inadequate, and 20 (54%) inadequate for significant subgroups. Main reasons for inadequacy were: wrong comparator (27 of 37 [73%], wrong endpoint 6 [16%] and use of historical controls (3 [11%]). For 34 (92%) the major disagreement also led to a lower benefit judgment. All 19 indirect treatment comparisons were considered flawed. Safety was a differentiator for 24 of the 59 submissions, either primary (2) or in addition to efficacy (22). G-BA disagreed with the manufacturer on safety for 12 (50%) of the 24 submissions. CONCLUSIONS This analysis of the first 3 years of G-BA’s early benefit appraisal illustrates that a majority of the submissions fail to convince the German authorities despite having obtained licensing approval. A wrong comparator was the main reason for full or partial rejection. Indirect treatment comparisons were never accepted. Decisions taken early in the development program have important repercussions on reimbursement negotiations with authorities in Germany.