Dry eye disease (DED) is common in Rheumatoid Arthritis (RA) patients. The application of conjunctival goblet cell count as a clinical biomarker to diagnose and respond to treatment can take place in rheumatoid arthritis patients under TNF-inhibitors (TNFi) therapy. This study aimed to investigate the ocular surface parameters and the long-term effects of TNFi therapy on ocular surface features and goblet cell count of rheumatoid arthritis patients. At baseline, rheumatoid arthritis patients eligible to TNFi were compared to healthy controls (similar age/gender), regarding Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear break-up time test, vital dye staining of the ocular surface, and conjunctival impression cytology. DED severity grade, impression cytology score, and goblet cell count were analyzed. Rheumatoid arthritis patients were followed after three (3 M) and 12 months (12 M), during TNFi treatment. Sixteen rheumatoid arthritis patients and 24 controls were compared: a higher frequency of abnormal OSDI (68.8% vs. 16.7%, p = 0.002), Schirmer's test < 10 mm (37.5% vs. 8.3%, p = 0.042), meibomian gland dysfunction (50% vs. 8.3%, p = 0.007), abnormal impression cytology (75% vs. 8.3%, p < 0.001), and mild to moderate DED (81.3% vs. 4.2%, p < 0.001) were observed in rheumatoid arthritis patients, who also had lower goblet cell count [325 (274-707) cells/mm2 vs. 742 (562-863) cells/mm2, p = 0.004]. The presence of Meibomian gland dysfunction was associated with higher disease activity scores (p < 0.05). The prospective early observation of these patients at 3 M showed an increase improvement in tear production by Schirmer's test [13 (7.5-17.5) vs. 23.5 (16-35); p = 0.001], and an improvement in impression cytology score [1 (0.5-2) vs. 1 (0-1), p = 0.031] and in goblet cell count [325 (274-707) vs. 931 (656-1,244), p < 0.001]. Eight RA responders to TNFi were also re-evaluated at 12 M with further improvement in goblet cell count [393 (275-827) vs. 872 (502-1,185) vs. 1,079 (867-1,244), p = 0.047]. Multifactorial DED is frequent in RA patients, comprising aqueous, lipid, and mucin components. TNFi prompt improves tear production and recovers the goblet cells, which can be a biomarker of the pathological process and response to therapy in this population.