The paper presents a new approach to developing an optical fiber refractometer. The objective of the study is to come up with a relatively inexpensive but reliable optical refractometer that can be used to measure the change of refractive index in a resolution of 10 −5 and to work in a dynamic range up to 6×10 −3 at a DC frequency of up to 100 Hz. It is known that the phase modulations of optical fiber sensors are very sensitive to external disturbances, especially to the effects of thermal drifts or vibrations. A cancellation technique to compensate the effect of variation on a PZT stack is proposed in this paper to stabilize the system. Two parallel Fabry–Perot sensing cavities corresponding to two path-matching cavities for read-out systems are employed to form path-matching differential interferometries (PMDI). One Fabry–Perot cavity is used as sensing head, and the other as reference sensor. As a result, the experimental data show that the change of refractive index of a so designed sensing system can be kept in at the level of 10 −4 without any serious variations even for a 3-h long-term monitoring. Accordingly, the proposed new system can be easily implemented and used as a long-term monitoring system in a medical care environment.