Background: Ruxolitinib is a JAK1/JAK2 inhibitor with demonstrated success in treating MF intermediate to high-risk patients, although the implications for low-risk disease classes are not yet established. Objective: To evaluate the effect of ruxolitinib on spleen size reduction and symptom burden in patients with low- and intermediate-1 risk primary myelofibrosis, and to analysis the relationship between baseline hematologic parameters and treatment response. Methods: A cross-sectional study was carried out on 30 patients diagnosed with primary myelofibrosis who were treated at the Hematology consultant/Merjan teaching hospital between January and August 2025. Patients were classified according International Prognostic Scoring System (IPSS). Ruxolitinib treatment was initiated at doses of 15–20 mg twice per day and therapeutic response was assessed after a minimum of six months. The main outcomes studied were reduction in spleen size (%) (estimated by ultrasound measuring the longest axis) and alterations in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Statistical evaluations were performed using Jamovi version 2.6.44, establishing significance at p < 0.05. Results: Among the 30 patients, 14 (46.7%) were classified as low-risk, while 16 (53.3%) were considered in the intermediate-1 risk category. The median baseline spleen sizes recorded were 20 cm for the low-risk group and 18.5 cm for the intermediate-1 group. After treatment, the median reduction in spleen size was 17.9% in low-risk compared to 15.4% in intermediate-1 group (p = 0.16). Moreover, an average decrease in the MPN-SAF TSS was 71.7% in the low-risk group as well as 66.4% in the intermediate-1 group (p = 0.52). There were no significant correlations in these data between initial hematologic parameters and treatment outcomes. Conclusion: Ruxolitinib therapy resulted in reduction of splenic size and symptom severity for patients with lower-risk myelofibrosis (MF). However, the variations observed between different International Prognostic Scoring System (IPSS) categories were not statistically significant. These results underscore the possible advantages of initiating ruxolitinib therapy earlier for symptomatic low-risk MF patients and point to the necessity for larger prospective studies to confirm these findings.