Abstract Background Polypharmacy is common in older people and associated with potential harms. The aim of this study was to analyse the characteristics of an older multimorbid population with polypharmacy and to identify factors contributing to excessive polypharmacy in these patients. Methods This cross-sectional analysis is based on the PRIMA-eDS trial, a large randomised controlled multicentre study of polypharmacy in primary care. Patients’ baseline data were used for analysis. A number of socioeconomic and medical data as well as SF-12-scores were entered into a generalized linear mixed model to identify variables associated with excessive polypharmacy (taking ≥10 substances daily). Results Three thousand nine hundred four participants were recruited. Risk factors significantly associated with excessive polypharmacy were frailty (OR 1.45; 95% CI 1.22–1.71), > 8 diagnoses (OR 2.64; 95% CI 2.24–3.11), BMI ≥30 (OR 1.18; 95% CI 1.02–1.38), a lower SF-12 physical health composite score (OR 1.47; 95% CI 1.26–1.72), and a lower SF-12 mental health composite score (OR 1.33; 95% CI 1.17–1.59) than the median of the study population (≤36.6 and ≤ 48.7, respectively). Age ≥ 85 years (OR 0.83; 95% CI 0.70–0.99) led to a significantly lower risk for excessive polypharmacy. No association with excessive polypharmacy could be found for female sex, low educational level, and smoking. Regarding the study centres, being recruited in the UK led to a significantly higher risk for excessive polypharmacy compared to being recruited in Germany 1/Rostock (OR 1.71; 95% CI 1.27–2.30). Being recruited in Germany 2/Witten led to a slightly significant lower risk for excessive polypharmacy compared to Germany 1/Rostock (OR 0.74; 95% CI 0.56–0.97). Conclusions Frailty, multimorbidity, obesity, and decreased physical as well as mental health status are risk factors for excessive polypharmacy. Sex, educational level, and smoking apparently do not seem to be related to excessive polypharmacy. Physicians should especially pay attention to their frail, obese patients who have multiple diagnoses and a decreased health-related quality of life, to check carefully whether all the drugs prescribed are evidence-based, safe, and do not interact in an unfavourable way. Trial registration This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).