Abstract Background and Aims Drug adherence is critically important for patients on thiopurines. We examined whether nurse-provided medication guidance improves drug adherence to thiopurines and clinical activity in patients with inflammatory bowel disease (IBD). Methods IBD outpatients taking a stable dose of thiopurines for 1 year were enrolled. After a baseline survey including the Morisky Medication Adherence Scale (MMAS)-8, nurses provided medication guidance to each patient using a specialized leaflet. The same survey was conducted 2 and 6 months after the guidance. Results Among 110 enrolled patients, 74 met the analysis criteria. In the low adherence group (MMAS-8 <6), the median MMAS-8 score significantly increased from 4 (range 1–5.75) to 5.25 (2–7) at 2 months (P = .0135) to 5.625 (2.5–7.75) at 6 months (P = .0004), but not in overall or the high adherence group (MMAS-8 ≥6). Older age (≥43 years, odds ratio [OR] = 5.63, 95% confidence interval [CI]: 1.59–19.9, P = .0074) and shorter disease duration (<129 months, OR = 6.78, 95% CI: 1.77–26.0, P = .0052) were independently associated with high adherence. Although clinical activity scores did not change during the observation period, the overall mean corpuscular volume (MCV) level significantly increased from 92.3 fL (61.4–105.5) to 92.5 (73.7–107.8) at 2 months (P = .0288) and 93.9 (74.4–107.6) at 6 months (P = .0062). MCV levels significantly increased in the low adherence group at 6 months (92.2 [72.2–105.5] to 94.0 [74.4–107.6], P = .0392) and tended to increase in the high adherence group (92.3 [61.4–101.2] to 93.6 [74.9–99.7], P = .0651). Conclusions Nurse-provided medication guidance improved drug adherence to thiopurines in IBD patients with low adherence and can also benefit those with high adherence.