Background: Osteoporosis is "a systemic metabolic bone disease characterized by low bone mass and micro architectural deterioration with a consequent increase in bone fragility with susceptibility to fracture. Multiple drug therapy with Alendronate, Calcium & plain vitamin D or alfacalcidol has been established to treat osteoporosis. In any patient with healthy liver and kidneys, plain vitamin D is expected to be as good as more active form of vitamin D. This study was conducted to compare the efficacy, safety and cost effectiveness between alfacalcidol and plain vitamin D in addition to Calcium and Alendronate in the management of osteoporosis. Methods: The Randomized Controlled Trial was conducted in B.P. Koirala Institute of Health Sciences, a tertiary care hospital in Eastern Nepal, over a period of twelve months from January 2013 to December 2014. Patient in group A were given Alfacalcidol, and group B were given plain Vitamin D. Results: Most of the patients were from the age group 60-69 yrs of age; mean age 65.54 ± 7.49. The BMD and T score were recorded at baseline and after treatment. The BMD measured 0.62853±.060241 at baseline and 0.67910 ± 0.059040 after treatment and T score measured -3.204 ±0.5455 at baseline and -2.698 ± 0.5772 after treatment. There is no statistical significance between the parameters (BMD and T score) of the two groups. Conclusion: For the first time in Nepal we have shown that the therapy with alfacalcidol and plain vitamin D when used with alendronate and calcium, have similar efficacy and safety, though the cost of the treatment with alfacalcidol was much higher than that of the plain vitamin D group.Keywords: Alfacalcidol, BMD, efficacy, osteoporosis, T-score, vitamin D IntroductionOsteoporosis is "a systemic metabolic bone disease characterized by low bone mass and micro architectural deterioration with a consequent increase in bone fragility with susceptibility to fracture. Primary osteoporosis is defined as osteoporosis that occurs in an individual who has no endocrinopathy or other disease state that would account for the changes in bone mass. A study done in 1997 projected that 1.2 million women in the UK have osteoporosis, 7.8 million in US. Up to 40% of women and 13% of men will have an osteoporotic fracture in their lifetime. With an aging world population osteoporotic fracture is expected to become an epidemic, rising from1.66 million in 1990 to 6.26 million by 2050.[1] Skeletal bone mass is represented by bone mineral density, (BMD), approximations. Dual-energy X-ray absorptiometry (DEXA) is the gold standard for quantifying BMD, because it is easily performed and is the most extensively validated test against fracture outcomes. DEXA scans allow osteoporosis to be diagnosed prior to fracture. In 1994, the World Health Organization, WHO, advocated the use of T scores to provide quantitative diagnostic criteria for osteoporosis. T scores represent the number of standard deviations (SD) away from the estimated peak bone mass for a normal young adult. Z scores...