Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many methods to assess adherence are subjective or have limitations. (Nac‐)5‐aminosalicylic acid (5‐ASA) urinalysis by high‐performance liquid chromatography (HPLC) seems feasible and reproducible in healthy volunteers. We performed a prospective study in adult quiescent UC patients to evaluate the feasibility of spot (Nac‐)5‐ASA urinalysis by HPLC to assess adherence in daily inflammatory bowel disease (IBD) care. Twenty‐nine patients (51.7% male, mean age 52 ± 11 years) were included (median FU 9 months) and weekly spot urine samples were collected. We found large variation in spot (Nac‐)5‐ASA urinary excretion that was unrelated to brand, dosing schedule or dosage of 5‐ASA. In conclusion, spot (Nac‐)5‐ASA urinalysis is not applicable to assess 5‐ASA adherence in daily IBD care.