Lyophilization is an important and well-established pharmaceutical drying process. Product temperature is the most critical process parameter during lyophilization as it impacts both product quality and process efficiency. Traditionally, thermocouples (TCs) or resistance temperature detectors (RTDs) and recently, manometric temperatures measurements (MTMs) have been used to monitor the product temperature. But, all of these techniques have several drawbacks. The objective of this study was the implementation and evaluation of an optical fiber system as novel process monitoring tool during lyophilization. Therefore, temperature profiles of mannitol, sucrose, or trehalose were recorded with various prototypes of the optical fiber sensors (OFSs) and compared to data obtained with conventional TCs or Pirani/capacitance manometry with respect to the endpoint of primary drying. The OFS allowed easy handling and easy center bottom positioning. Data obtained with the OFS in contact with product were in good agreement with data obtained via TCs or Pirani/capacitance manometry. The OFSs showed significantly higher sensitivity, faster response, and better resolution compared to TCs. This allowed for the detection of additional excipient crystallization events. It was found that force effects on unshielded sensors enabled to detect glass transitions. Three-dimensional temperature profiles were obtained with an OFS helix configuration. The possible integration of a glass fiber with several OFSs in series into the shelf surface enables non-invasive, automatic loading compatible monitoring of the drying process. In conclusion, these advantages turn the novel optical fiber systems into a highly attractive process monitoring tool during lyophilization.