Background: Smoking is a recognized risk factor for ocular surface disease, yet its cytological effects are less well studied. This study evaluated conjunctival impression cytology (CIC) changes in chronic smokers and correlated them with ocular surface morbidity. Methods: A prospective case–control study included 80 male smokers (≥20 pack-years) and 80 age-matched non-smokers. Symptom assessment (DEQ-5) and clinical evaluation (TBUT, Schirmer’s I/II, tear meniscus height, corneal staining, corneal sensitivity) were performed. CIC was undertaken in smokers with corneal staining ≥A1D2 and graded using Nelson’s system. Results: Smokers had significantly higher ocular morbidity than controls (DEQ-5 ≥6: 85% vs 12.5%; TBUT <10 s: 52.5% vs 12.5%; Schirmer’s I <10 mm: 20% vs 6.3%; Schirmer’s II <10 mm: 23.8% vs 10%; all p<0.05). Corneal staining was observed in 11.25% of smokers, none in controls. Of five smokers undergoing CIC, three (60%) showed pathological changes (grade 2), while two (40%) had grade 0–1; no grade 3 changes were observed. Pathological CIC consistently correlated with abnormal symptoms, reduced TBUT, low Schirmer’s values and reduced corneal sensitivity. Conclusion: Chronic smoking causes conjunctival cytological alterations paralleling ocular surface morbidity. CIC is a simple, non-invasive adjunct that can detect early cellular damage and supports preventive strategies such as smoking cessation.