The objectives of this study are to evaluate a new semi-quantitative (0-5) musculoskeletal ultrasound (US) erosion score in patients with rheumatoid arthritis (RA) and to prove its usefulness in the detection of disease activity and success of therapy. Thirty-eight patients with RA (mean disease duration 10.1 ± 11.9 years) were enrolled. Start or change of therapy (DMARD/biologics) was an inclusion criterion. DAS28, laboratory (ESR and CRP) and US data were evaluated before new therapy initiation and after 1, 3, 6 and 12 months. Thirteen joints of the clinically more affected hand and forefoot (wrist and MCP, PIP, MTP joints 2-5) were analyzed for synovitis in grayscale (GS) and power Doppler (PD) US, tenosynovitis/paratenonitis in GS/PDUS (wrist, MCP level) and for erosions. Erosions were analyzed by a new semi-quantitative score (grade 0, no erosion; grade 1, <1 mm, grade 2, 1 to <2 mm; grade 3, 2 to ≤3 mm; grade 4, >3 mm; grade 5, multiple bone erosions). After 12 months, DAS28 decreased from 4.5 to 3.4 (p < 0.001), the synovitis score in GSUS from 26.3 to 12.8 (p = 0.001) and the synovitis score in PDUS from 10.6 to 4.1 (p < 0.001). The erosion score decreased from 21.5 to 18.1 (p = 0.046). There were longitudinal significant correlations between the new erosion score and both the DAS28 (r = 0.368; p = 0.025) and the synovitis score in PDUS (r = 0.365; p = 0.026) over a 1-year follow-up period. The new erosion score might be a useful tool for the evaluation of erosive changes by US in RA patients. In the course of DMARD and biologic therapy, it was responsive under 1-year follow-up examination.