We assessed the relative sensitivities of standard (SD)- and triple-dose (TD) gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) for detecting enhancing lesions in different phases of multiple sclerosis (MS) disease activity. Ten MS patients were studied with monthly brain MRI scans for a 3-month follow-up (i.e., 4 scans were obtained for each patient with both SD and TD). A total of 11 relapses were recorded and treated with short-term high-dose steroid therapy. Enhancing lesion numbers and volumes were significantly higher for TD vs. SD scans (p < 0.0001). For both Gd doses, the numbers and volumes of lesions were higher during clinical relapses; the differences were statistically significant when comparing the results for scans obtained during and after a relapse. The gain in sensitivity of TD vs. SD scans for enhancing lesion detection was lower during relapses, whilst it was maximum after relapses, although these differences did not reach statistical significance. Our data confirm the potential role of TD MRI for monitoring MS activity, since, with its higher sensitivity, it may detect more subtle blood-brain barrier (BBB) damage. They also suggest that the degree of BBB damage in individual lesions changes during different phases of disease activity.