Use of active optical sensors (AOS) in nitrogen (N) management of row crops continues to grow. Since the first studies in the mid-1990s, several commercial AOS are now available. Typically, canopy reflectance in red and near infrared (NIR) bands are used to calculate the normalized difference vegetation index (NDVI). More recently, commercially available AOS include a third, red-edge band that allows the calculation of additional vegetation indices (VIs). We present two studies of five site-years of N management studies in Maricopa, AZ, on a Casa Grande sandy loam with cotton (Gossypium hirsutum L.). The 2014-2015 study was conducted under an overhead sprinkler irrigation system (OSI), and the 2016-2018 study was in subsurface drip irrigation (SDI). The study objective was to compare the ability of 12 different VIs to detect N deficiency among N treatments from shortly after emergence to midbloom. In the OSI study, which showed delayed, small N treatment effects, NDRE and the chlorophyll index using amber (CIRE) detected N deficiency in zero-N and in reduced N-reflectance-based plots 7-23 d before other VIs did. With SDI, the choice of VI was less critical as several VIs could distinguish N deficiency in zero-N and in reflectance plots. The commonly used NDVI red (NDVIR) only detected N deficiency in reflectance plots in one of five site-years. In conclusion, we recommend the use of AOS with NIR and red-edge bands and the calculation of NDRE or CIRE to guide AOS-based in-season N management of irrigated cotton.