Lung ultrasound (LUS) and high-resolution computed tomography (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a one-year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes. SSc-ILD patients who started NIN were enrolled and followed for twelve months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after one year and quantitatively analysed with CALIPER software. Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after twelve months (from 175.1 ± 66.7-120.8 ± 70.3 for BL, p= 0.005 and from 50.6 ± 32.5-37.2 ± 22.4 for PLI, p= 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction of both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (p= 0.016 and p= 0.04, respectively) and Saint George's Respiratory Questionnaire (p= 0.006 and p= 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after twelve months of NIN, thus paralleling the stabilization obtained at pulmonary function tests. We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed.