Aim: To compare the long term (6 months) effect of once daily dose of Timolol in Gel Forming Solution (GFS) with twice daily dose of Timolol in aqueous solution, in control of Intra Ocular pressure (IOP), in cases of Primary Open Angle Glaucoma (POAG). Material and methods: In a Prospective, Randomized Clinical trial, POAG or Ocular Hypertension patients diagnosed between April 2008 and September 2012 were studied. 750 eyes of 600 patients with age group 46-79 yrs. were selected. Diurnal variation of Tension (DVT) was done along with other investigations. Patients were divided into two groups A and B randomly. Group A was started on Timolol twice daily and group B on once daily Timolol GFS. 400 eyes of 310 patients were started on Timolol solution eye drops twice a day.120 eyes of 100 patients were lost to follow-up or unresponsive to timolol (8 eyes of 5 patients). 350 eyes of 290 patients were started on Timolol GFS once daily, of which 70 eyes of 50 patients were lost to follow up or unresponsive to timolol (7 eyes of 5 patients).So finally, after 6 months treatment, in Group A, 280 eyes of 210 patients and in Group B 280 eyes of 240 patients were analyzed. Analysis was done under following headings. Amount of reduction of IOP at various timings of the day by Timolol and Timolol GFS, Amount of reduction of mean IOP by Timolol and Timolol GFS, Amount of reduction of peak IOP by Timolol and Timolol GFS, Change in systemic parameters after 6 months of treatment. Comparison was done between the two groups with respect to amount of IOP reduction at each time of the day, reduction in 'mean' IOP, and reduction in 'peak' IOP. 't' test was used for analysis. Observations: In group A, the mean IOP before the treatment, at 8 am, 10 am, 12 noon, 2 pm, 4 pm, 6 pm, 8 pm, 10 pm, 12 am, 2 am, 4 am and 6 am decreased by 8.5±2.40, 8.85±2.68, 10.17±2.18, 10.32±2.05, 10.03±2.28, 9.28±3.04, 8.71±3.00, 8.36±2.31, 9.18±2.22, 9.39±1.96, 9.07±2.18 and 9.18±2.39 respectively with P value at each time of 0.00, showing that Timolol twice daily is effective in bringing down IOP. In group B, the mean IOP for the corresponding times came down by 7.95±2.40, 8.75±2.33, 9.49±1.64, 9.52±2.06, 8.93±2.50, 8.27±3.24, 7.59±3.04, 8.35±2.03, 8.36±2.36, 8.63±1.96, 8.45±1.98 and 7.30±2.86 respectively with P value at 0.00 showing that the Timolol GFS with OD dose significantly brings down the IOP. When the reduction in Mean IOP at the above timings were compared between group 1 and 2, the P values obtained were 0.402, 0.878, 0.192, 0.156, 0.092, 0.236, 0.171, 0.995, 0.188, 0.156, 0.275, 0.114 which shows that there is no statistical difference between two groups. Mean reduction in Pulse, systolic BP and diastolic BP were 3.07 ± 1.39 , 2.64 ± 2.04 and 2.21±1.66 with P values of <0.001 for all three, in group A and 0.39 ± 1.23 0.57 ± 2.43 and 0.50 ± 2.01 respectively with P values of 0.10,0.22 and 0.20 in group B. The p value in intergroup comparison was <0.001 for all three parameters, showing that the Timolol GFS has less significant effect on systemic parameters. The mean percentage of missed doses in group A was 13.53±4.27 and in group B was 8.67± 6.33. P value was 0.002 suggesting that the patient, missing the medicine dosage is significantly high in group A. Conclusions: Once daily dosage of Timolol in Gel Forming Solution is equally efficacious as twice daily timolol with less systemic effects and more compliance.