Nintedanib, an intracellular inhibitor targeting multiple tyrosine kinases, has emerged as a standard treatment for various fibrotic lung diseases. Despite its efficacy, side effects such as nausea, diarrhea, and hepatotoxicity often lead to dose reduction or discontinuation. In this retrospective analysis at an university hospital's interstitial lung disease clinic, we aimed to identify baseline characteristics associated with dose adjustment or treatment discontinuation. Of the 58 patients included, 41.4% maintained the full nintedanib dose, while 31.0% required dosage reduction, and 27.6% discontinued treatment due to adverse events, predominantly gastrointestinal and hepatotoxic effects. Multivariate analysis revealed body surface area (BSA) as an independent and significant baseline risk factor (adjusted Odds Ratio [aOR] 0.22), suggesting a 78% decreased chance of requiring dose modification for every decimal point increase in BSA. A BSA cutoff of ≤1.73 m [2] exhibited a sensitivity of 73% and specificity of 91.7%, with significant impact on one-year survival under full-dose treatment (p < 0.001). Lower BSA was associated with early onset adverse effects, particularly gastrointestinal, supporting the need for regular clinical monitoring. The study emphasizes the importance of recognizing baseline factors to ensure the safety and tolerability of nintedanib, thereby preventing the progression of pulmonary fibrosis. These findings contribute to the evolving understanding of nintedanib management in fibrotic interstitial lung diseases, guiding clinicians in personalized treatment approaches.