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In simultaneous pancreas-kidney transplantation (SPKT), persistence or recurrence of pancreatic autoantibodies (PAs) has been associated with pancreas graft (PG) autoimmune-driven injury. Our aim was to analyze the impact of PAs on PG survival. Between January 1, 2000, and December 31, 2017, we studied 139 patients with post-SPKT anti–glutamic acid decarboxylase (GAD) autoantibody. Alloimmune (ALI) events were defined as PG rejection and/or de novo donor-specific antibodies (DSA). Hence, 3 groups were defined: patients without ALI events or anti-GAD (n = 42), those with ALI events (n = 14), or those only with autoimmune events (positive for anti-GAD and no ALI events; n = 83). Male sex was predominant (n = 72, 52%). Median age was 35 years (interquartile range: 31-39) and median follow-up was 6-7 years (interquartile range: 4.1-9.2). Regarding anti-GAD positivity post-SPKT (n = 90, 65%), no differences were observed concerning age, sex, anti-HLA antibodies, HLA mismatch number and de novo DSA. ALI events were present in 10% (n = 14). PG survival 15 years post-SPKT was better in patients without immune events (96%) followed by those with ALI (69%) and autoimmune events (63%) (P =.025). Anti-GAD was associated to higher annualized mean Hb1AC (P =.006) and lower mean C-peptide (P =.013). According to pre- and post-SPKT anti-GAD status, conversion from negative to positive was associated to worse (63%) 10-year PG survival (P =.044), compared to persistence of negative (100%) or positive anti-GAD (88%). Anti-islet cell and anti-insulin autoantibodies had no impact. Anti-GAD presence post-SPKT was associated to higher pancreas disfunction and lower PG survival. De novo anti-GAD seems to offer a particular risk of PG failure. • Autoimmune and alloimmune events have a negative impact on pancreas graft survival. • Autoantibody conversion is associated with a high risk of developing insulin-dependent diabetes mellitus after simultaneous pancreas-kidney transplantation. • Worse function of the pancreas graft and lower survival in SPKT are strongly associated to emergence of anti–glutamic acid decarboxylase (GAD). [ABSTRACT FROM AUTHOR]