Homeopathic medicines were never subjected for long term safety follow up since its inception. They were effective in the treatment of range of diseases based on the principal of symptom similarity. Nevertheless treatment with homeopathic medicines in practise and principles can give rise to few safety issues like Schein’s symptoms (symptoms of excess medicine), conjoint malady and incurable disease other than its usual pathogenetic phenomena. The objective of present investigation was carried to demonstrate the safety of use of homeopathic formulation more than single medicine at a time (polypharmacy) in suitable doses and repetitions. This was retrospective design aimed to study rate of occurrence of different parameters like Schein’s symptoms, conjoint malady and incurable diseases after polypharmaceutical prescription of homeopathic remedies. Data was expressed as odds ratio and relative risk for all the three variables namely, schein’s symptoms, conjoint malady and sub curable disease. Total of 635 cases studied with nearby equal proportion of both sexes [(355 (55.9%) males and 280 (44.1%) females] from all age groups including paediatric age group 20 (3.14%). Treated conditions were chronic headaches, alopecia areata, urolithiasis, hypothyroidism and benign prostatic hyperplasia [BPH] 33 (5.2%), diabetes mellitus [DM] 27 (4.25%). Background therapy of conventional medicine was not found to be discontinued for the hypothyroidism and diabetes mellitus. The relative risk and odds ratio for Schein symptoms, conjoint malady and incurable disease were 2.554, 3.647, 2.242 and 15.310, 57.652, 6.383. In conclusion, use of homeopathic polypharmaceutical formulations was found to be safe and associated with minimal risk (P < 0.0001).