This randomised control trial studied newly diagnosed glaucoma patients given mono‐ or multi‐therapy regarding differences in initial intraocular pressure (IOP) reduction, target IOP levels reached and influence of untreated baseline IOP on IOP reduction. Patients newly diagnosed with manifest primary open‐angle glaucoma and included in the Glaucoma Intensive Treatment Study (GITS) were randomised to immediate intensive treatment with any of three different IOP‐lowering substances supplied in two bottles plus 360° laser trabeculoplasty or to conventional stepwise treatment starting with a single drug. Intraocular pressure reduction was analysed one month after initiation of treatment. One hundred and eighteen patients (143 eyes) received mono‐therapy and 122 patients (152 eyes) multi‐therapy. Median baseline IOP was similar in both groups at 24.0. After one month, values for median IOP reduction were 6.3 (range: −5.3–31.0) in the mono-therapy and 11.0 (range: 0.7–34.5) mmHg in the multi-therapy group. The mean relative decline was 26.8 (range: −32.0–55.4) and 46.0 (range: 4.6–81.6) % (p=0.000). A larger proportion of the multi‐therapy patients reached each target IOP level (p=0.000). The higher the baseline IOP, the larger the observed pressure reduction, considering both absolute and relative figures. The effect was more pronounced in eyes with multi‐therapy than in those with mono‐therapy (p=0.000). For every mmHg higher IOP at baseline, the IOP was reduced by an additional 0.56 (mono‐therapy) or 0.84 (multi‐therapy) mmHg. Intensive treatment led to considerably greater IOP reduction than mono‐therapy. Among patients with IOP ≥30mmHg at diagnosis, an IOP of <16 was reached in 2/3 of those with multi‐therapy but in none with mono‐therapy. The IOP reduction was highly dependent on the untreated IOP level. Further studies on the impact of early intensive therapy on the progression of glaucoma visual fields, as well as the incidence of adverse effects, is needed prior to introducing the multi-therapy approach to intraocular pressure control.