BACKGROUND: Several drugs have been linked to the risk of microscopic colitis (MC), a condition characterised by watery, non-bloody diarrhoea. Antibiotics can induce similar symptoms, but their connection to MC remains unclear. AIM: To investigate the antibiotic-related risks of MC in adults aged 65 years and older. METHODS: This was a nationwide, self-controlled case series study including adults aged >/= 65 years with a new prescription for antibiotics and biopsy-confirmed, incident MC (Sweden, 2007-17). We identified cases from the nationwide histopathology cohort ESPRESSO individually linked to several registers. Using conditional Poisson regression, we estimated incidence rate ratios (IRR) for four risk periods: on treatment, and 1-14, 15-91, and 92-365 days post-treatment, compared with the non-treatment periods in the same individual. We also conducted a negative control outcome analysis to assess whether the association was specific to MC or due to diagnostic workup. E-values were used to assess robustness to unmeasured confounding. RESULTS: We identified 2393 persons with incident biopsy-confirmed MC (median age at diagnosis 74; 67% women). Compared with the non-treatment periods, the risk of MC in the age-adjusted analysis increased with antibiotic treatment (IRR: 1.44 [95% CI: 1.13-1.84], E-value: 2.24), 1-14 days (IRR: 1.12 [0.83-1.49]), 15-91 days (1.12 [0.97-1.31]) and 92-365 days post-treatment (1.19 [1.07-1.32]). The negative control outcome analysis showed similar risks of biopsy-confirmed normal mucosa after antibiotic use. CONCLUSION: The observed association between antibiotic use and MC may result from detection bias rather than a causal relationship.