The aim of this study was to compare the handgrip strength (HGs), assessed with a cylindrical-shape grip device, of fibromyalgia syndrome (FM) patients with healthy subjects and to demonstrate the relationship between HGs characteristics and disease severity. Consecutive female patients with FM were enrolled and compared to a group of healthy women. The correlations between HGs curve characteristics and disease severity indices were studied through the Spearman’s rho correlation coefficients (rho). The HGs threshold distinguishing the FM presence was determined using the receiver operating characteristic (ROC) curves analysis. Multivariate regression analysis was used in order to assess the contribution of covariates on the HGs. 110 patients (mean age 53.8 ± 12.4 years) and 111 healthy controls have been enrolled. Altogether all parameters related to the analysis of HGs were worse in patients with FM. The HGs cut-off distinguishing the presence of a FM was 14.2 Kg. A negative correlation was found between disease severity indices and peak force (p < 0.001). Factors significantly associated with HGs area under the curve (AUC) in multivariate analysis were the Widespread Pain Index (WPI) (p = 0.003) and the revised Fibromyalgia Impact Questionnaire (FIQR) (p = 0.016). HGs is reduced in female FM patients and is inversely related to disease severity. The force-time curves analysis may be used as a complementary tool in the FM assessment and monitoring.