Background End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response. Objective Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients’ adherence to diary use and characteristics associated with adherence. Methods A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed. Results Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P<.001). No significant association was found between adherence and gender (P=.84), age (P=.22), or education level (lower education level: P=.58, middle education level: P=.46, versus high education level), while higher anxiety scores were associated with lower adherence (P=.03). Adherence to the online questionnaires was also high (>99%). Missing data due to technical issues were limited. Conclusions The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.