Fabry disease is an inherited disorder of glycolipid metabolism with progressive involvement of multiple organs, including the gastrointestinal tract, in classically affected male patients. Clinical presentations in males with later-onset Fabry phenotypes are more heterogeneous and largely dependent on the level of residual α-galactosidase A activity. We assessed agalsidase beta treatment outcomes of gastrointestinal symptoms in adult males with classic or later-onset Fabry disease. Self-reports of abdominal pain and diarrhea (‘present’/’not present’ since previous assessment) at last clinical visit (≥0.5 year of follow-up) were compared with treatment-baseline. Classic male patients were considerably younger at first treatment than the fewer males with later-onset phenotypes (36 vs. ~47 years) and reported gastrointestinal symptoms more frequently at baseline (abdominal pain: 56% vs. 13%; diarrhea: 57% vs. 23%). As compared with baseline, significantly fewer classic patients reported abdominal pain after a median of 4.7 years of treatment (N = 171, 56% vs. 41%, P < 0.001). Moreover, significantly fewer patients reported diarrhea after 5.5 years of follow-up (N = 169, 57% vs. 47%, P < 0.05). Among the males with later-onset phenotypes, albeit statistically non-significant, abdominal pain reports reduced after a median of 4.2 years (N = 48, 13% vs. 4%) and diarrhea reports reduced after a median of 4.4 years of treatment (N = 47, 23% vs. 13%). Sustained treatment with agalsidase beta was associated with improvement in abdominal pain and diarrhea in a significant proportion of classic male Fabry patients. Males with later-onset phenotypes reported gastrointestinal symptoms much less frequently at baseline as compared with classic patients, and non-significant reductions were observed. •GI symptoms significantly reduced in classic male Fabry patients on agalsidase beta.•Treatment was started long after symptoms began; earlier initiation is recommended.•Fabry-unrelated causes should be excluded if GI symptoms persist on treatment.•GI symptoms were much less prevalent among males with later-onset Fabry disease.