Advanced remote sensing techniques and regional algorithms are combined to produce and analyze a 12-year multi-sensor time series of bio-optical properties for the Adriatic Sea. First, a multi-sensor series of normalized water-leaving radianceLWNis created with an optically-based merging technique applied to SeaWiFS and MODIS data, then distributions of inherent optical properties (IOPs) are obtained with a semi-analytical bio-optical model. Additionally, Chlais computed by two regional empirical algorithms associated with two classes of optical properties representative of open ocean waters and Adriatic coastal regions (Classes 1 and 2, respectively). The domain of applicability of each algorithm is dynamically determined on the basis of theLWNinput spectrum by a novelty detection approach. The various satellite products are validated using a comprehensive bio-optical time series collected in the northern Adriatic. At the basin level, the frequency of occurrence of Classes 1 and 2 are 61% and 10%, respectively, with Class 2 waters particularly located in the northern part and characterized by higher levels of Chlaand IOPs. The annual cycle of Chlaover the 12-year period exhibits significant variations in amplitude and phase; moreover, the annual cycle shows a reduced amplitude during a period centered on 2004 for a time interval that varies with the region. In the northern Adriatic, the overall level of Chlaappears lower between 2003 and 2008 compared to the beginning of the series.