Abstract Background Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. Methods A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. Results In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p